A snake venom antigen epitope chimera, antibodies and preparation method and use thereof
By constructing and recombinantly expressing snake venom antigen epitope chimeras, high-purity nanobodies were obtained, solving the problems of high immunoreactivity and complex purification of existing anti-snake venom immunoglobulins derived from equine plasma, and achieving highly efficient protection against a variety of snake venoms with low side effects.
Patent Information
- Application Number
- CN202111425418.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-11-26
- Publication Date
- 2025-10-24
- Estimated Expiration
- 2041-11-26
AI Technical Summary
Existing antivenom immunoglobulins are mainly derived from horse plasma, which presents problems such as high immune response, complex purification, and difficulty in addressing the differences in snake venom composition in different regions and seasons.
A chimeric snake venom antigen epitope was constructed, and linear antigen epitopes containing multiple snake venom toxins were recombinantly expressed. High-purity nanobodies were obtained after immunizing alpacas. Multivalent nanobodies and bivalent antibodies were prepared by octanoic acid precipitation and ultrafiltration purification techniques.
The obtained nanobodies exhibit high specificity and stability against various snake venoms, with low side effects, effectively protecting against snake bites from a variety of common highly venomous snakes. The purification process is simple and yields high purity.
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Figure CN116178560B_ABST
Abstract
Description
Technical fields:
[0001] This invention belongs to the field of biomedicine, specifically relating to a snake venom antigen epitope chimera, its antibody, preparation method, and uses. Background technology:
[0002] Snakes belong to the order Squamata, suborder Serpentes, and are classified into three suborders and eleven families according to the current classification system. These include: the suborder Blind Snakes (Blind Snakes, Heterodactyls, and Slender Blind Snakes); the suborder Proserpentes (Pythons, Tubularia, Pintails, Endospermia, and Scrophularia); and the suborder Colubridae (Colombia, subdivided into several subfamilies), the Elapidae (Elapheinae, Pyrocodae, and Hymenophora), and the Viperidae (White-headed Viperinae, Viperinae, and Viperinae). Except for most of the Colubridae, all snakes in this suborder are venomous. There are over 3,340 species of snakes worldwide, with over 660 venomous species, nearly 200 of which are deadly. There are over 1,700 species of Colubrids, of which over 100 contain small amounts of venom or are of low venom quality, and a very small number are potentially fatal. my country has over 210 species of snakebites, belonging to 9 families and 66 genera, including over 60 venomous snakes, of which over 10 are highly venomous (2018 Chinese Expert Consensus on Snakebite Treatment, Expert Group on Chinese Expert Consensus on Snakebite Treatment). Common venomous snakes in my country include: A. Elapidae: cobra, king cobra, krait, banded krait; B. Viperidae: viper, pit viper, pit viper, bamboo viper; Sea snakes: 16 species including the blue-ringed sea snake (Chinese venomous snakes and snakebite treatment, 2008 Blue Ocean).
[0003] Snake venom is one of the most complex and concentrated naturally occurring high-potency toxins in nature. The venom is typically a pale yellow or milky white, translucent, viscous liquid containing over 100 components. Each type of snake venom contains multiple different toxic components, and the content of these components varies significantly between different snake venoms. Even within the same species of snake, the toxic components can differ due to geographical distribution, seasonality, and the snake's age. Snake venom components include enzymes, polypeptides, glycoproteins, and metal ions, with dozens of toxic proteins comprising 90-95% or more of the total venom. Snake venom can damage the nervous system, blood system, muscle tissue, circulatory system, urinary system, endocrine system, and digestive system.
[0004] With the development of proteomics, the venom of various venomous snakes has been isolated, purified, and its components determined. For example, the venom of spectacled snakes mainly contains snake venom metalloprotease (SVMP), phospholipase A2 (PLA2), and three-finger toxin (3FT). Specifically, the venom of the banded krait contains 66% PLA2, 3.5% SVMP, 1.8% 3FT, and other proteins; the venom of the cobra contains 12% PLA2, 1.6% SVMP, 84% 3FT, and other proteins; while the venom of the king cobra contains 2.8% PLA2, 11.9% SVMP, 64.5% 3FT, and other proteins (a review and database of snake venom proteomes, 2017, Theo Tasoulis and Geoffrey K. Isbister). This shows that even within the same family of venomous snakes, the content of each type of toxin varies greatly.
[0005] Antivenom immunoglobulins are widely recognized as the most effective drugs for treating snake bites. Currently, the primary source of most antivenom immunoglobulins worldwide remains the isolation of polyclonal antibodies from hyperimmune equine plasma. Over a century ago, the production process underwent three major technological improvements, evolving from crude to refined antisera: from crude antiserum products targeting venom (i.e., first-generation antitoxins) to highly purified immunoglobulins (i.e., second-generation antitoxins), and then to monovalent Fab or bivalent F(ab')2 fragments obtained by digestion with trypsin or pepsin, salting out, or affinity chromatography to remove the Fc terminus of immunoglobulin IgG (i.e., third-generation antitoxins). In my country, the Shanghai Institute of Biological Products began developing antivenom serum in the 1950s, subsequently developing anti-viper venom serum, anti-five-step snake venom serum, anti-cobra venom serum, anti-viper venom serum, anti-golden banded krait venom serum, and anti-silver banded krait venom serum (Current Status and Strategies of Antivenom Immunoglobulin Drug Development, Tian Jing, 2015). To date, only Shanghai Seren Biotechnology Co., Ltd. produces snake venom antitoxins in my country, and it has marketed four monovalent liquid formulations of snake venom antitoxins, namely monovalent immunoglobulin F(ab')2 molecules against viper venom, five-step snake venom, cobra venom, and silver banded krait venom.
[0006] In 1993, Hamers-Casterman et al. from the Free University of Brussels first reported the existence of another type of antibody in camel blood, besides traditional IgG antibodies, called nanobody. This antibody typically consists of only 110-130 amino acids, with a molecular weight of only 12-15 kDa, far smaller than traditional intact antibodies (150-160 kDa) and their Fab fragments (approximately 50 kDa), yet it possesses similar or higher specific antigen affinity to traditional antibodies. The inherent characteristics of single-domain antibodies—small molecular weight, stable physicochemical properties, high affinity, and ease of recombinant expression—lead to lower immunogenicity compared to traditional mouse monoclonal antibodies or horse antiserum; their injection into humans can produce a weaker immune response. Summary of the Invention:
[0007] To obtain better anti-snake venom immunoglobulin substances, it is first necessary to construct chimeras that can serve as one or more snake venom antigens. Therefore, in one aspect, the present invention provides a snake venom antigen epitope chimera containing one or more of the sequences described below: SEQ ID NO: 14-34.
[0008] In some embodiments, SEQ ID NO:14 to 34 are linked by a linker peptide; the linker peptide is selected from one or more of GG, GGG, KK, and GGGS.
[0009] In some embodiments, the amino acid sequence contains an amino acid sequence having at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to the amino acid sequence shown in SEQ ID NO:37 or SEQ ID NO:39.
[0010] In some embodiments, the amino acid sequence contains an amino acid sequence having at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to the amino acid sequence shown in SEQ ID NO:2 or SEQ ID NO:4.
[0011] Further, its nucleotide sequence is a nucleic acid sequence containing at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to the nucleic acid sequence shown in SEQ ID NO:41 or SEQ ID NO:43.
[0012] Further, its nucleotide sequence is a nucleic acid sequence containing at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to the nucleic acid sequence shown in SEQ ID NO:6 or SEQ ID NO:8.
[0013] In some embodiments, the amino acid sequence contains an amino acid sequence having at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to the amino acid sequence shown in SEQ ID NO:9.
[0014] Secondly, the present invention also provides an antibody or antigen-binding fragment, which is obtained by immunizing a fragment containing a snake venom antigen epitope chimera as described above as an antigen, wherein the antibody or antigen-binding fragment specifically binds to the venom of the banded krait, the silver krait, the cobra, and the king cobra.
[0015] Furthermore, the antibody or antigen-binding fragment specifically binds to PLA2. Furthermore, the antibody or antigen-binding fragment also specifically binds to SVMP and 3FT.
[0016] In some embodiments, the antibody or antigen-binding fragment is a nanobody and is prepared by immunizing alpacas.
[0017] Thirdly, the present invention also provides a monoclonal antibody or antigen-binding fragment that specifically binds to the PLA2 protein in snake venom and includes three complementarity-determining regions; the sequences of the three complementarity-determining regions are shown in SEQ ID NO:44, SEQ ID NO:45 and SEQ ID NO:46, or in SEQ ID NO:47, SEQ ID NO:48 and SEQ ID NO:49.
[0018] In some embodiments, the amino acid sequence contains an amino acid sequence having at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to the amino acid sequence shown in SEQ ID NO:10 or SEQ ID NO:11.
[0019] In some embodiments, the nucleic acid sequence is a nucleic acid sequence containing at least 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% homology to the nucleic acid sequence shown in SEQ ID NO:12 or SEQ ID NO:13.
[0020] Fourthly, the present invention also provides a method for preparing the antibody or antigen-binding fragment as described in the second aspect above, wherein after immunizing alpacas, blood is collected, precipitated with caprylic acid, and then purified by membrane ultrafiltration.
[0021] Furthermore, the membrane ultrafiltration purification specifically involves: first ultrafiltration with a 100KD ultrafiltration membrane, and then ultrafiltration with a 30KD ultrafiltration membrane.
[0022] Fifthly, the present invention also provides a method for preparing a monoclonal antibody or antigen-binding fragment as described in the third aspect above, wherein an amino acid sequence as shown in SEQ ID NO:9 is linked to KLH, immunized with alpacas and screened for phage libraries, and expressed as a bivalent specific monoclonal antibody or antigen-binding fragment.
[0023] In a sixth aspect, the present invention provides the use of the antibody or antigen-binding fragment as described in the second aspect above in the preparation of diagnostic agents and / or therapeutic agents for bites from kraits, cobras, and / or king cobras.
[0024] In a seventh aspect, the present invention provides the use of the monoclonal antibody or antigen-binding fragment as described in the third aspect above in the preparation of diagnostic agents and / or therapeutic agents for bites from kraits, cobras, and / or king cobras.
[0025] As used herein, the term "recombinant protein" refers to an artificially designed / constructed protein, rather than a naturally occurring protein. The "recombinant" in "recombinant protein" of this invention does not represent its production method; it is used only to indicate that the "recombinant protein" does not exist naturally. The recombinant protein of this invention can be an expressed protein or an assembled protein.
[0026] As used herein, the terms “treatment,” “therapeutic,” and “curative” are used interchangeably. The term “treatment” includes controlling the progression of a disease, symptom, condition, and associated symptoms, preferably reducing the impact of the disease, symptom, condition, or alleviating one or more symptoms of the disease, symptom, condition. This term includes curing the disease or completely eliminating the symptoms. This term includes symptom relief. This term also includes, but is not limited to, non-curative palliative treatment. The term “treatment” includes administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising the recombinant protein or fusion protein of the present invention to prevent or delay, reduce, or alleviate the progression of a disease, symptom, condition, or the impact of one or more symptoms of the disease, symptom, condition.
[0027] As used herein, the term "administration" refers to the delivery of a therapeutically effective amount of a pharmaceutical composition comprising the recombinant protein or fusion protein of the present invention to a subject. Administration can be systemic or local. Administration can be performed using an administration device, such as a syringe. Methods of administration include, but are not limited to, implantation, nasal inhalation, spraying, and injection. Routes of administration include inhalation, intranasal administration, oral administration, intravenous administration, subcutaneous administration, or intramuscular administration.
[0028] Conventional antibodies or immunoglobulins are heterotetraglycoproteins of approximately 150,000 Daltons with the same structural characteristics, composed of two identical light chains (L) and two identical heavy chains (H). However, alpaca antibodies (nanobodies) lack light chains, and the heavy chains also lack a constant region 1. The antibodies used in this article are broadly defined, including both conventional antibodies or immunoglobulins and alpaca antibodies. Alpaca antibodies are derived from alpacas and are called nanobodies due to their small size.
[0029] Invention Content 1: Prediction and Screening of Linear Antigenic Epitopes for Three Types of Toxins
[0030] From four common venomous snakes in my country (Najanajaatra), the king cobra (Ophiophagus hannah), and the krait (Bungarus fasciatus), three major types of venom toxins were selected as research subjects. First, all PLA2, SVMP, and 3FT amino acid sequences of the krait, cobra, and king cobra were downloaded from databases. Sequence alignment or phylogenetic analysis was performed, and finally, linear antigenic epitope prediction was conducted.
[0031] The obtained predicted linear epitopes were further optimized according to the following principles: A. to include as many of the obtained predicted antigenic epitopes as possible; B. to include as many conserved sequences of each protein class as possible based on homology alignment; C. to cover as many linear antigenic epitopes of each snake venom protein class as possible in the linear antigenic epitopes of each venom protein class; the sequences in Table 4 were obtained.
[0032] Table 4. 21 selected predicted antigenic epitopes
[0033]
[0034]
[0035] Summary of the Invention 2: Screening different combinations of different antigenic epitopes
[0036] Different tandem arrangements were used for the sequences in Table 4. Common arrangements include: A) Tandem arrangements of the predicted antigenic epitopes for each type of toxin, then tandem them together to form a chimera, i.e., tandem arrangements of the 7 PLA2, 7 SVMP, and 8 3FT epitopes, followed by the tandem arrangement of the three large fragments; B) Alternating arrangements of the 21 predicted antigenic epitopes; C) Arrangements according to molecular size; D) Interleaved arrangements of the sequences, taking into account the size of the linking peptides. This invention ultimately adopted arrangement D.
[0037] According to the four AD schemes, the predicted linear antigenic epitopes were linked together to form a snake venom antigenic epitope chimera, which was then recombinantly expressed. After the expression product was used to immunize mice, the superior form was screened by enzyme-linked immunosorbent assay (ELISA) for use in the following alpaca immunization.
[0038] Invention Content 3 yielded an active multivalent nanobody and a bivalent anti-PLA2 antibody.
[0039] The serum obtained after immunizing alpacas with the above-expressed snake venom epitope chimera as an antigen was active.
[0040] The serum was precipitated with caprylic acid to obtain high-purity antibodies.
[0041] Pharmacodynamic testing showed that the antibody was a multivalent nanobody and was active.
[0042] After linking SEQ ID NO:9 with KLH, serum was obtained from immunized alpacas to construct a phage library. After screening the phage library, SEQ ID NO:11 and SEQ ID NO:10 were selected from the obtained sequences to construct a bivalent antibody, which was active.
[0043] This invention selects the main toxins PLA2, SVMP, and 3FT from the venom of three highly venomous snakes in the family Elaphe spp. (King Cobra, Banded Krait, and Cobra), and uses software to predict 21 linear antigenic epitopes. These predicted linear antigenic epitopes are expressed as snake venom antigenic epitope chimeras. The expression products are used to immunize alpacas, yielding active multivalent nanobodies. After purification, the purity of these antibodies can reach over 90%. After immunizing alpacas with the chimera expressing the predicted PLA2 linear antigenic epitope, the sequence is obtained through phage display experiments, constructing a bivalent specific antibody.
[0044] The beneficial effects of this invention are as follows: First, the recombinant tandem expression of antigenic epitopes produces an immunogenic product that overcomes the toxicity of naturally derived snake venom and the differences in venom composition from different regions, snake ages, and even different seasons, ensuring the stability of the immunogenic antigen. Second, the resulting multivalent nanobodies provide protection against the venoms of four common highly venomous snakes in the Spectacularidae family, with low side effects. Therefore, the antigen preparation method of this invention is ingeniously designed, and the antiserum purification is simple and easy, yielding high-purity, biologically active nanobodies. This method can be extended to the development of other antiserums. Attached image description:
[0045] Figure 1 This is a homology comparison of the PLA2 amino acid sequences of the venom of the banded krait, cobra, and king cobra.
[0046] Figure 2 This is a homology comparison of the SVMP amino acid sequences of the venom of the banded krait, cobra, and king cobra.
[0047] Figure 3 It is an evolutionary tree of 3FT proteins in the venom of the banded krait, cobra, and king cobra.
[0048] Figures 4(a)-(d) show the conserved sequence alignments of the first, second, fifth, and sixth branches of the 3FT phylogenetic tree of the venom of the banded krait, cobra, and king cobra, respectively.
[0049] Figure 5 This is the predicted result of the PA2B6-BUNFA antigenic epitope.
[0050] Figure 6 This is the prediction result of the VM3_BUNFA antigenic epitope.
[0051] Figures 7(a)-(c) show the epitope prediction results for I (taking 3SXZ_OPHHA as an example), II (taking 3SO8_NAJAT as an example), and VI (3NO24_OPHHA) of the 3FT protein, respectively.
[0052] Figure 8 This is an SDS-PAGE map of snake venom epitope chimera expression. AD represents the recombinant expression product of the snake venom epitope chimera AD, and M is the protein marker (purchased from Bio-Rad #161-0377). The molecular weights from top to bottom are: 250, 150, 100, 75, 50, 37, and 25 KD.
[0053] Figure 9 It is HPLC detection of nanobodies. Detailed implementation method:
[0054] To facilitate understanding of the invention, reference will be made to certain embodiments below, and specific language will be used to describe the invention. However, it should be understood that these specific embodiments are not intended to limit the scope of the invention. Any changes and further modifications to the described embodiments, as well as any further applications of the invention, are those commonly conceived by those skilled in the art.
[0055] All reagents not specifically mentioned in this embodiment can be purchased commercially.
[0056] Example 1: Linear antigenic epitope prediction of PLA2, SVMP, and 3FT in the venom of the banded krait, cobra, and king cobra.
[0057] 1.1 Downloading and Homology Comparison of PLA2, SVMP, and 3FT Sequences of Three Snakes
[0058] In the UniProtKB library ( www.uniprot.org Using the search term "PLA2 fasciatus AND reviewed:yes", a total of 12 PLA2 sequences were found, 10 of which were snake venom PLA2 sequences. Using the search terms "PLA2 "najaatra" AND reviewed:yes" and "PLA2 "Ophiophagus hannah" AND reviewed:yes", three sequences were found for each. These sequences are summarized in Table 1, and their conserved sequence intervals were analyzed. Figure 1 .
[0059] Similarly, "SVMP fasciatus AND reviewed:yes" and "SVMP "Ophiophagus hannah" AND reviewed:yes" each yielded one sequence, while "SVMP "naja atra" AND reviewed:yes" yielded six sequences. One fragment was removed, leaving five sequences, which were then summarized in Table 2. Conserved sequence interval analysis yielded... Figure 2 .
[0060] Similarly, "three-finger toxin" fasciatus AND reviewed: yes yielded 8 results; "three-finger toxin" "naja atra" AND reviewed: yes yielded 42 results; and "three-finger toxin" "ophiophagus hannah" AND reviewed: yes yielded 44 results. These were then summarized in Table 3. Figure 3 Phylogenetic analysis was performed on the sequences to obtain... Figure 3Based on evolutionary relationships, these 94 3FT proteins were divided into six groups, I-VI. Among them, groups III and IV contain only 3FT proteins from king cobra and cobra, respectively, while groups I, II, V and VI contain 3FT proteins from all three snake species. Therefore, homologous sequence alignment was further performed on groups I, II, V and VI, resulting in Figures 4(a), 4(b), 4(c) and 4(d).
[0061] Table 1. Amino acid sequences of PLA2 venom from banded krait, cobra, and king cobra.
[0062]
[0063]
[0064] Table 2. SVMP amino acid sequences of venom from the banded krait, cobra, and king cobra.
[0065]
[0066]
[0067] Table 3
[0068]
[0069]
[0070]
[0071]
[0072]
[0073]
[0074]
[0075] 1.2 Epitope Prediction of PLA2, SVMP, and 3FT Sequences
[0076] Antigen prediction was performed in the IDEB database (http: / / tools.immuneepitope.org / bcell / ), using PA2B6-BUNFA as the prediction target. Four positions were predicted, and those with a threshold greater than 0.5 were selected. Figure 5 The following are examples: NIPPQ (SEQ ID NO:35) 11-15, YCGPGGTGTPLD 44-54, and KPDITCTGAKGSCG 90-102. 11-15 is the signal peptide motif and is therefore not considered. Additionally, epitopes predicted to be less than 5 amino acid residues were also not considered.
[0077] Similarly, using VM3_BUNFA as the prediction target, the results of predicting antigenic epitopes with more than 5 amino acid residues ( Figure 6 The following are listed: 24-50 VVYPQKVPSLPKGGVQNPQPETKYEDT, 72-96 LFSEDYTETHYASDGREITTSPSVQ, 152-160 NVEEEDETP, 169-176 TWESDEPF, 415-421 DCGSPRD, and 574-581 DDPNYGMV.
[0078] Similarly, in the epitope prediction of 3FT, Group I used 3SXZ_OPHHA as the prediction target, and the results are shown in Figure 7(a): QTCEP 31-35 and SCPTEK 61-65; Group II used 3SO8_NAJAT as the prediction target, and the results are shown in Figure 7(b): SRTPETTEIC 29-38 and ELRPT 68-72; Group VI used 3NO24_OPHHA as the prediction target, and the results are shown in Figure 7(c): AATCPEAKS 64-72; while no epitope was predicted in Group V.
[0079] 1.3 Identifying candidate antigenic epitopes
[0080] From a homology perspective, 44YCGPGGTGTPLD54 of PA2B6-BUNFA is the location of a conserved sequence in all PLA2 sequences, while another sequence, 108CDRAAAICFAAAPY121, also shows high homology. However, 90KPDITCTGAKGSCG102 shows poor homology. Therefore, we consider adding more sequences: GKLTCKADNDECAAF of PA2N3_BUNFA, SGGTITCNADNDE of PA2HA_BUNFA, and SQGTLTCKGGNNA of PA2A_NAJAT. A total of six candidate epitopes are proposed for expression.
[0081] In SVMP, the epitope sequences used for expression are: 24VVYPQKVPSLPKGGVQNPQPETKYEDT50, 72LFSEDYTETHYASDGREITTSPSVQ96, 152NVEEEDETP160, 169TWESDEPF176, 415DCGSPRD421, and 574DDPNYGMV581 for VM3_BUNFA. Additionally, the epitope sequences KIRVYEMINAVNTKFRPLKIH for VM3KL_NAJAT and RMRVFDMVNYITVVYKALNIH for VM3_OPHHA are also used.
[0082] Similarly, in 3FT, 3SXZ_OPHHA has 31QTCEP35 and 61SCPTEK65; 3SO8_NAJAT has 29SRTPETTEIC38 and 68ELRPT72; and 3NO24_OPHHA has 64AATCPEAKS72. Additionally, 3SOFL_NAJAT has PKNSALLKYVCCSSDNK and 3SDC9_OPHHA has PKSSADVEVLCCDTNK, totaling seven epitope sequences used for expression.
[0083] All candidate sequences are summarized in Table 4.
[0084] Example 2: Predicted tandem expression of antigenic epitopes (snake venom antigenic epitope chimera)
[0085] 2.1 Carrier Construction
[0086] The sequences in Table 4 were linked together using GGG, GG, and KK linker peptides, and several expression schemes were adopted:
[0087] ① The predicted antigenic epitopes of each type of toxin were tandemly linked, and then linked together to form a chimera. Specifically, the epitopes of 7 PLA2, 7 SVMP, and 8 3FT were first tandemly, and then the three large fragments were tandemly linked; as shown in SEQ ID NO:1, the expression product was named the A snake venom antigenic epitope chimera. The ten H's at the end of SEQ ID NO:1 represent the tag protein. Removing the H's from the tag protein results in SEQ ID NO:36.
[0088] ② The 21 predicted antigenic epitopes were arranged alternately; as shown in SEQ ID NO:2, the expression product was named B snake venom antigenic epitope chimera. The 10 H's at the end of SEQ ID NO:2 represent the tag protein. Removing the H tags results in SEQ ID NO:37.
[0089] ③ Arranged according to the number of amino acids in each epitope; as shown in SEQ ID NO:3, its expression product is named C snake venom antigen epitope chimera. The 10 H's at the end of SEQ ID NO:3 are tag proteins. Removing the H tag proteins results in SEQ ID NO:38.
[0090] ④ The sequences are interleaved, and the size of each sequence and the linked peptide is considered, as shown in SEQ ID NO:4. The expression product is named D snake venom antigen epitope chimera. The ten H's at the end of SEQ ID NO:4 represent the tag protein. Removing the H's from the tag protein results in SEQ ID NO:39.
[0091] The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns of the above four snake venom antigenic epitope chimeras are shown below. Figure 8 .
[0092] Based on the codon bias of *E. coli*, SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, and SEQ ID NO:4 were optimized into SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:8. These sequences were sent to a professional company for gene synthesis. Then, using NdeI and XhoI enzymes, the A, B, C, and D chimeras were inserted into the vector pET30a(+) and transformed into BL... 21 (DE)3. After removing the H tag and TGA stop codon from SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8, we get SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42 and SEQ ID NO:43 respectively.
[0093] 2.2 Recombinant expression in Escherichia coli
[0094] 1. BL that has already been genetically modified 21 (DE)3 was streaked on LB agar plates containing 50 μg / ml kan and incubated overnight at 37°C.
[0095] 2. Pick a single colony and inoculate it into 20 ml of LB medium containing 100 μg / ml kan, and incubate overnight at 37°C with shaking at 220 rpm.
[0096] 3. Add 1L of LB medium to a 5L Erlenmeyer flask, then inoculate with 20ml of the cell culture that has been cultured overnight. Incubate at 37°C on a shaker until OD600 = 0.6-0.8, then add 1mM IPTG and incubate at 220rpm for 5 hours.
[0097] 4. Centrifuge to collect bacterial cells, add 100 ml of pH 8.0, 20 mM Tris-HCl, 100 mM NaCl, and 20 mM imidazole buffer to resuspend the bacterial cells, and then sonicate on ice for 10 min.
[0098] 5. Centrifuge the cell lysate after sonication at 4°C and 12000g for 20 min, and collect the supernatant.
[0099] 2.3 Purification of recombinant tandemly expressed proteins
[0100] Purification was performed using IMAC Sepharose 6Fast Flow gel, referencing GE Life Sciences' "Affinity Chromatography".
[0101] Following the operating instructions of the nano (Thermo Scientific), the protein concentration of each expression product was determined.
[0102] Example 3: Chimeric Immunization of Mice and Potency Detection
[0103] 3.1 Immunization of chimeric mice
[0104] Twelve adult Kunming mice were randomly divided into four groups, each injected with a chimeric snake venom epitope (A, B, C, or D), corresponding to groups A, B, C, and D, respectively. The initial immunization consisted of 20 μg / mouse of the chimeric snake venom epitope A, B, C, and D, mixed with an appropriate amount of Freund's adjuvant, emulsified using a sterile syringe, and then injected. Two weeks later, a second immunization was performed, using incomplete Freund's adjuvant instead of complete Freund's adjuvant. The dosage of the chimeric snake venom epitope A, B, C, and D remained 20 μg / mouse. This second immunization was repeated four times (two weeks apart), i.e., one initial immunization and four second immunizations. Blood was then collected intravenously, and the serum from three mice in each group was mixed in equal volumes for ELISA to detect the immunogenicity of each chimeric snake venom epitope.
[0105] 3.2 ELISA
[0106] Equal volumes of venom from banded kraits, silver kraits, cobras, and king cobras were mixed. 100 μl of 0.05 mol / L pH 9.6 carbonate buffer containing 5 μg of the venom mixture was added to each well of a 96-well plate, and the plate was incubated overnight at 4°C. The plate was then blocked with 250 μl of blocking buffer [30% BSA (5% sucrose and 5% lactose)] at 37°C for 2 h. Positive sera were diluted 100, 200, 400, 800, and 1600 times with pH 7.4 phosphate buffer, and negative sera (sera from mice not immunized with the antigen) were diluted the same as the positive sera. 100 μl of each dilution was added to each well, and each dilution was repeated in triplicate. The average value was recorded, and the reaction group with the highest positive-to-negative A450 ratio (P / N value) was selected as the best antigen.
[0107] Results: After the serum was diluted 800 times, the OD450 readings of the AD group were 1.0, 1.2, 0.75 and 1.6 respectively. The chimera of the D group had the highest immunogenicity and was used for subsequent alpaca immunization to prepare nanobodies.
[0108] Example 4: Generation and purification of nanobodies
[0109] 4.1 Alpaca Immunization
[0110] The immunization procedure was roughly as follows: multiple subcutaneous injections of antigen were performed on the alpaca's neck, with 300 μg of D snake venom antigen epitope chimera injected each time. A total of 5 immunizations were administered (one immunization every two weeks). One week before immunization and two weeks after the last immunization, 5 mL of blood was collected from the jugular vein, centrifuged at 3500 r / min for 15 min, and the supernatant serum was collected into a clean EP tube for plasma titer testing. Then, 100 mL of blood was collected and purified according to Example 4.2.
[0111] 4.2 Plasma Purification
[0112] Take 100ml of plasma stock solution, add 200ml of ultrapure water, slowly add n-octanoic acid stock solution dropwise to make the final concentration 5%, and adjust the pH value to maintain it between 5 and 6; stir evenly at room temperature and let stand for 1 hour.
[0113] The supernatant of B was centrifuged at 4°C for 20 minutes at 12,000 rpm / min to obtain the supernatant;
[0114] C. Tandem Ultrafiltration: The supernatant of the filtered protein solution was ultrafiltered three times using a 100 kDa ultrafiltration membrane, and the filtrate was collected. The filtrate was then concentrated using a 30 kDa ultrafiltration membrane, and the concentrate was collected, replacing the supernatant with PBS buffer. The purified concentrate was analyzed by high-performance liquid chromatography (HPLC) as described in Example 4.3.
[0115] 4.3 HPLC detection
[0116] Referring to the Agilent 1200 Infinity II instruction manual and the 2015 edition of the Chinese Pharmacopoeia, a G3000SW chromatographic column (TOSOH Corporation, Japan) was used.
[0117] 1. Turn on the HPLC, wait for the instrument to perform a self-test, enter the workstation, select the method (set the wavelength to 280nm, column temperature to 25℃, flow rate to 0.6ml / min, and run time to 40min).
[0118] 2. Baseline run: First rinse with 10% acetonitrile, then replace with mobile phase containing (pH 7.0, 0.2 mol / L phosphate buffer containing 1% isopropanol) to equilibrate and run baseline.
[0119] 3. Preparation of test solution: Dilute the test sample with the mobile phase to a solution containing 12 mg of protein per 1 ml.
[0120] 4. Take 20 μl of each diluted test solution and inject it into the high performance liquid chromatograph for analysis. The running time is 40 min. The retention time is used for qualitative analysis, and the content is calculated using the area normalization method.
[0121] Results: Nanobodies with a purity of up to 90% can be obtained (see...) Figure 9 )
[0122] 4.4 ELISA detection of nanobody titers
[0123] Refer to Example 3.2 to perform the ELISA method, and use labeled Rabbit Anti-Illama IgG (Heavy Chain) antibody (GeneTex, GTX20276) as the secondary antibody.
[0124] Results: 10% of the venom of the banded krait was effective against... 6 Positive for krait venom (10) 3 Positive, cobra 10 5 Positive and King Cobra 10 5 Positive. Number 10 6 10 3 10 5 and 10 5 This indicates the strength of antibody activity in serum; the higher the value, the stronger the antibody activity. The experimental procedure is as follows: dilute the obtained nanobodies to achieve an OD450 value between 1 and 1.5. 6 This means that the antibody is diluted 10 times with the venom of the golden banded snake. 6 After dilution, the OD reaches 1-1.5. Similarly, for the silver-ringed snake diluted 10... 3 times, therefore 10 6 10 3 10 5 This represents the level of activity.
[0125] Example 5: Construction of Humanized Anti-PLA2 Plutonate Specific Antibody
[0126] Although this invention relates to immunizing alpacas, the PCR primers used to establish the phage library are human sequences, resulting in humanized antibodies, as described in the literature "A VHH That Neutralizes the Zinc Metalloproteinase Activity of Botulinum Neurotoxin Type A" (DOI: 10.1074 / jbc.M109.073163). Therefore, the anti-PLA2 embolus-specific antibody constructed in this embodiment is a humanized antibody.
[0127] 5.1 PLA2 Immunization Alpaca
[0128] The 44YCGPGGTGTPLD54, 108CDRAAAICFAAAPY121, and 90KPDITCTGAKGSCG102 of PA2B6-BUNFA, the GKLTCKADNDECAAF of PA2N3_BUNFA, the SGGTITCNADNDE of PA2HA_BUNFA, and the SQGTLTCKGGNNA of PA2A_NAJAT were linked together using a linker peptide to obtain the sequence SEQ ID NO:9. Then, SEQ ID NO:9 was outsourced to a company for synthesis and linked to keyhole limpet hemocyanin (KLH). Because SEQ ID NO:9 has a very small molecular weight, it is unlikely to produce a good immune response; therefore, it is generally coupled with a larger molecule such as BSA or KLH to enhance the immune effect.
[0129] Immunize alpacas according to the procedure in Example 4.1. Two weeks after the last immunization, 100 mL of blood was collected from the alpacas to isolate peripheral blood lymphocytes. Total RNA was extracted from the peripheral blood lymphocytes and reverse transcribed into cDNA using the AMV First Strand cDNA Synthesis Kit (Thermo Scientific, USA).
[0130] 5.2 Construction and Screening of Bacteriophages
[0131] Referring to the reference "A VHH That Neutralizes the Zinc Metalloproteinase Activity of Botulinum Neurotoxin Type A" (DOI: 10.1074 / jbc.M109.073163) and Example 2 of patent CN202010122406.2 "A Fully Humanized Bispecific Anti-Tetanus Antibody and Its Construction Method and Application", phage construction and screening were performed. Two sequences with good activity (SEQ ID NO:10 and SEQ ID NO:11) were selected for expressing the bivalent antibody, with corresponding nucleotide sequences SEQ ID NO:12 and SEQ ID NO:13.
[0132] Among them, CDR1, CDR2 and CDR3 in SEQ ID NO:10 are AASGRTFS (SEQ ID NO:44), AVSSWSVGT (SEQ ID NO:45) and SATYYTGEYYLVQADRYQH (SEQ ID NO:46), respectively.
[0133] CDR1, CDR2, and CDR3 in SEQ ID NO:11 are RDTYDSHC (SEQ ID NO:47), MNSDGSMT (SEQ ID NO:48), and KTRRTSAVNWLCRASGSDY (SEQ ID NO:49), respectively.
[0134] 5.3 Construction of tetravalent antibodies
[0135] Using the vector and experimental methods previously constructed by Shanghai Seron Biotechnology Co., Ltd. (see CN202010122406.2 "A Fully Humanized Bispecific Anti-Tetanus Antibody and Its Construction Method and Application"), the obtained tetravalent antibody was subjected to potency testing as described in Example 4.4.
[0136] Results: 10% of the venom of the banded krait was effective against... 5 Positive for krait venom (10) 2 Positive, cobra 10 3 Positive and King Cobra 10 3 Positive.
[0137] The preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims. sequence list <110> Shanghai Seren Biotechnology Co., Ltd. <120> A snake venom antigen epitope chimera, its antibody, preparation method, and uses <130> WHYY-NP-21-100928 <160> 165 <170> PatentIn version 3.5 <210> 1 <211> 323 <212> PRT <213> Artificial Sequence <400> 1 Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp Gly Gly Cys Asp 1 5 10 15 Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr Gly Gly Lys Pro 20 25 30 Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly Gly Gly Gly Lys 35 40 45 Leu Thr Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe Gly Gly Ser 50 55 60 Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu Gly Gly Ser Gln 65 70 75 80 Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Gly Gly Val Val Tyr 85 90 95 Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln Asn Pro Gln 100 105 110 Pro Glu Thr Lys Tyr Glu Asp Thr Gly Gly Leu Phe Ser Glu Asp Tyr 115 120 125 Thr Glu Thr His Tyr Ala Ser Asp Gly Arg Glu Ile Thr Thr Ser Pro 130 135 140 Ser Val Gln Gly Gly Asn Val Glu Glu Glu Asp Glu Thr Pro Gly Gly 145 150 155 160 Thr Trp Glu Ser Asp Glu Pro Phe Gly Gly Asp Cys Gly Ser Pro Arg 165 170 175 Asp Gly Gly Asp Asp Pro Asn Tyr Gly Met Val Gly Gly Lys Ile Arg 180 185 190 Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg Pro Leu Lys 195 200 205 Ile His Gly Gly Arg Met Arg Val Phe Asp Met Val Asn Tyr Ile Thr 210 215 220 Val Val Tyr Lys Ala Leu Asn Ile His Gly Gly Gln Thr Cys Glu Pro 225 230 235 240 Gly Gly Ser Cys Pro Thr Glu Lys Gly Gly Ser Arg Thr Pro Glu Thr 245 250 255 Thr Glu Ile Cys Gly Gly Glu Leu Arg Pro Thr Gly Gly Ala Ala Thr 260 265 270 Cys Pro Glu Ala Lys Ser Gly Gly Pro Lys Asn Ser Ala Leu Leu Lys 275 280 285 Tyr Val Cys Cys Ser Ser Asp Asn Lys Gly Gly Pro Lys Ser Ser Ala 290 295 300 Asp Val Glu Val Leu Cys Cys Asp Thr Asn Lys His His His His His 305 310 315 320 His His His <210> 2 <211> 323 <212> PRT <213> Artificial Sequence <400> 2 Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp Gly Gly Val Val 1 5 10 15 Tyr Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln Asn Pro 20 25 30 Gln Pro Glu Thr Lys Tyr Glu Asp Thr Gly Gly Gln Thr Cys Glu Pro 35 40 45 Gly Gly Cys Asp Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr 50 55 60 Gly Gly Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Ser Asp 65 70 75 80 Gly Arg Glu Ile Thr Thr Ser Pro Ser Val Gln Gly Gly Ser Cys Pro 85 90 95 Thr Glu Lys Gly Gly Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly 100 105 110<Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe Gly Gly Thr Trp Glu 145 150 155 160 Ser Asp Glu Pro Phe Gly Gly Glu Leu Arg Pro Thr Gly Gly Ser Gly 165 170 175 Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu Gly Gly Asp Cys Gly 180 185 190 Ser Pro Arg Asp Gly Gly Ala Ala Thr Cys Pro Glu Ala Lys Ser Gly 195 200 205 Gly Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Gly Gly 210 215 220 Asp Asp Pro Asn Tyr Gly Met Val Gly Gly Pro Lys Asn Ser Ala Leu 225 230 235 240 Leu Lys Tyr Val Cys Cys Ser Ser Asp Asn Lys Gly Gly Pro Lys Ser 245 250 255 Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn Lys Gly Gly Lys 260 265 270 Ile Arg Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg Pro 275 280 285 Leu Lys Ile His Gly Gly Arg Met Arg Val Phe Asp Met Val Asn Tyr 290 295 300 Ile Thr Val Val Tyr Lys Ala Leu Asn Ile His His His His His His 305 310 315 320 His His His <210> 3 <211> 323 <212> PRT <213> Artificial Sequence <400> 3 Gln Thr Cys Glu Pro Gly Gly Glu Leu Arg Pro Thr Gly Gly Ser Cys 1 5 10 15 Pro Thr Glu Lys Gly Gly Asp Cys Gly Ser Pro Arg Asp Gly Gly Thr 20 25 30 Trp Glu Ser Asp Glu Pro Phe Gly Gly Asp Asp Pro Asn Tyr Gly Met 35 40 45 Val Gly Gly Asn Val Glu Glu Glu Asp Glu Thr Pro Gly Gly Ala Ala 50 55 60 Thr Cys Pro Glu Ala Lys Ser Gly Gly Ser Arg Thr Pro Glu Thr Thr 65 70 75 80 Glu Ile Cys Gly Gly Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu 85 90 95 Asp Gly Gly Ser Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu [[ID=4३]]100 105 110 Gly Gly Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Gly 115 120 125 Gly Cys Asp Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr Gly 130 135 140 Gly Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly Gly 145 150 155 160 Gly Gly Lys Leu Thr Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe 165 170 175 Gly Gly Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr 180 185 190 Asn Lys Gly Gly Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys 195 200 205 Ser Ser Asp Asn Lys Gly Gly Arg Met Arg Val Phe Asp Met Val Asn 210 215 220 Tyr Ile Thr Val Val Tyr Lys Ala Leu Asn Ile His Gly Gly Lys Ile 225 230 235 240 Arg Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg Pro Leu 245 250 255 Lys Ile His Gly Gly Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr 260 265 270 Ala Ser Asp Gly Arg Glu Ile Thr Thr Ser Pro Ser Val Gln Gly Gly 275 280 285 Val Val Tyr Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln 290 295 300 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr His His His His His 305 310 315 320 His His His <210> 4 <211> 336 <212> PRT <213> Artificial Sequence <400> 4 Gln Thr Cys Glu Pro Gly Gly Glu Leu Arg Pro Thr Lys Lys Cys Asp 1 5 10 15 Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr Lys Lys Tyr Cys 20 25 30 Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp Gly Gly Gly Thr Trp Glu 35 40 45 Ser Asp Glu Pro Phe Gly Gly Asp Cys Gly Ser Pro Arg Asp Lys Lys 50 55 60 Val Val Tyr Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln 65 70 75 80 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr Gly Gly Gly Pro Lys 85 90 95 Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Ser Asp Asn Lys Gly 100 105 110 Gly Gly Ser Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Ser 115 120 125 Asp Gly Arg Glu Ile Thr Thr Ser Pro Ser Val Gln Gly Gly Gly Ser 130 135 140 Lys Ile Arg Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg 145 150 155 160 Pro Leu Lys Ile His Gly Gly Gly Gly Lys Leu Thr Cys Lys Ala Asp 165 170 175 Asn Asp Glu Cys Ala Ala Phe Gly Gly Gly Ser Arg Met Arg Val Phe 180 185 190 Asp Met Val Asn Tyr Ile Thr Val Val Tyr Lys Ala Leu Asn Ile His 195 200 205 Gly Gly Gly Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala 210 215 220 Lys Lys Ser Cys Pro Thr Glu Lys Gly Gly Asn Val Glu Glu Glu Asp 225 230 235 240 Glu Thr Pro Gly Gly Asp Asp Pro Asn Tyr Gly Met Val Gly Gly Gly 245 250 255 Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn Lys 260 265 270 Gly Gly Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly 275 280 285 Lys Lys Ser Arg Thr Pro Glu Thr Thr Glu Ile Cys Gly Gly Gly Ser 290 295 300 Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu Gly Gly Gly Ala 305 310 315 320 Ala Thr Cys Pro Glu Ala Lys Ser His His His His His His His His 325 330 335 <210> 5 <211> 972 <212> DNA <213> Artificial Sequence <400> 5 tattgtggtc ctggtggtac tggtactcca ctggatggtg gttgtgatcg tgcagctgcc 60 atttgtttcg ctgcagcgcc gtatggtggt aaaccggaca ttacctgtac tggtgccaaa 120 ggtagctgtg gtggcggtgg caaactgacc tgtaaagcag ataatgatga atgcgctgct 180 ttcggtggct ctggtggcac catcacctgc aacgcggata acgatgaagg cggttctcag 240 ggcaccctga cttgcaaagg tggcaacaac gcgggtggcg tcgtttaccc gcagaaagtt 300 ccatccctgc cgaaaggcgg cgtgcaaaac ccgcagccag aaaccaaata cgaggacacc 360 ggcggtctgt tttccgaaga ctataccgaa acccattacg ctagcgacgg ccgtgagatt 420 actacttctc cgagcgtaca gggtggcaac gttgaagagg aagatgagac cccgggcggt 480 acttgggaaa gcgacgaacc gtttggtggt gattgcggct ctccgcgtga tggcggtgat 540 gatccgaact acggcatggt tggtggcaag atccgtgtgt acgaaatgat caacgcggtg 600 aacaccaaat tccgtccact gaaaatccac ggtggccgta tgcgtgtgtt cgacatggtg 660 aactacatca ccgtagttta taaagcgctg aacatccacg gcggccagac ttgcgaacca 720 ggtggtagct gcccgactga gaaaggcggt tctcgtaccc cggaaacgac tgaaatttgt 780 ggtggtgaac tgcgtccgac tggtggtgca gcaacctgtc cggaagctaa atctggcggt 840 ccgaagaact ccgcgctgct gaaatatgtt tgctgctcct ccgataacaa aggtggcccg 900 aaatcttctg cagatgtcga agttctgtgc tgtgatacca ataagcacca tcaccaccac 960 catcaccact ga 972 <210> 6 <211> 972 <212> DNA <213> Artificial Sequence <400> 6 tattgcggtc ctggtggtac tggtactcca ctggatggtg gtgttgtta tccgcagaaaa 60 gttccgtctc tgccaaaggg tggcgttcag aacccgcagc ctgaaaccaa atacgaagat 120 acgggcggtc agacctgtga accgggtggt tgcgatcgtg cggctgctat ctgttttgcc 180 gcagcgccgt atggtggtct gttttctgaa gattacaccg aaacccacta cgcttctgac 240 ggtcgtgaaa tcaccacttc cccttctgtg cagggtggct cttgcccaac tgagaaaggt 300 ggcaaaccgg acattacctg taccggtgcc aaaggttcct gcggtggtgg caatgtagaa 360 gaggaagacg aaaccccggg tggttctcgt accccggaga ctaccgaaat ttgcggtggt 420 ggcaaactga cctgtaaagc cgataacgac gaatgcgcag cttttggcgg cacctgggaa 480 agcgatgaac cttttggtgg cgaactgcgt ccgactggtg gttccggtgg cactatcacc 540 tgcaacgcgg acaacgacga aggcggtgat tgtggttctc cgcgtgatgg cggtgctgca 600 acctgtccag aagcaaagtc tggtggcagc cagggtaccc tgacctgtaa aggtggcaat 660 aacgctggcg gcgatgaccc aaactatggt atggtaggtg gtcctaaaaa ctccgctctg 720 ctgaaatacg tgtgctgcag ctctgataac aaaggtggtc cgaagtctag cgctgatgtc 780 gaagttctgt gctgcgacac taacaaaggc ggcaaaatcc gtgtttacga aatgattaac 840 gcagttaaca ctaaattccg tccgctgaaa atccacggtg gtcgtatgcg tgttttcgac 900 atggttaact acatcacggt agtgtataaa gctctgaaca tccatcatca ccaccaccat 960 caccatcatt ga 972 <210> 7 <211> 972 <212> DNA <213> Artificial Sequence <400> 7 caaacttgtg aaccgggtgg tgaactgcgt ccaactggtg gttcttgtcc gacggaaaaa 60 ggtggcgatt gcggttctcc gcgtgatggt ggcacttggg aaagcgatga accgttcggt 120 ggtgacgatc cgaactacgg tatggtgggt ggtaacgttg aagaagaaga tgaaactcct 180 ggtggtgcag cgacttgtcc ggaagcgaaa agcggtggta gccgtactcc tgaaaccacc 240 gaaatttgtg gcggttattg tggtccaggc ggtaccggta cccctctgga tggtggtagc 300 ggcggtacta ttacctgcaa cgcagacaac gacgaaggcg gttctcaggg tactctgacc 360 tgtaaaggtg gtaacaacgc gggtggttgc gatcgtgctg ctgccatttg cttcgctgca 420 gcaccgtatg gcggtaaacc ggatatcacc tgcaccggcg ctaaaggttc ttgcggtggt 480 ggcggtaaac tgacttgtaa agcggataac gatgagtgtg cagcctttgg tggcccgaaa 540 agctccgcgg acgttgaagt tctgtgctgt gataccaaca aaggtggtcc gaaaaacagc 600 gcactgctga aatatgtttg ttgttcttcc gacaacaaag gcggtcgtat gcgtgtgttc 660 gatatggtta actacatcac cgtggtttac aaggcgctga acattcacgg cggtaagatc 720 cgtgtttacg aaatgatcaa cgctgttaac actaaattcc gcccgctgaa aatccacggt 780 ggtctgttct ccgaggacta tactgaaacc cattacgcgt ctgacggccg tgaaatcacc 840 accagcccgt ccgttcaggg tggtgttgta tacccacaga aagttccgtc tctgccgaag 900 ggtggtgtgc aaaacccgca gccagaaacc aatacgaag acacccacca ccaccaccac 960 caccaccact ga 972 <210> 8 <211> 1014 <212> DNA <213> Artificial Sequence <400> 8 cagacttgtg aacctggtgg cgaactgcgt ccgaccaaaa agtgtgatcg tgctgcagca 60 atttgtttcg cggctgcgcc gtataagaaa tactgtggtc cgggtggtac cggtactcct 120 ctggatggtg gtggtacctg ggaaagcgat gaaccattcg gcggtgactg tggttctccg 180 cgtgacaaaa aagttgtgta tcctcagaaa gttccgagcc tgcctaaggg cggtgttcag 240 aacccgcagc ctgaaacgaa atacgaagat actggtggtg gtccgaaaaa ctctgcgctg 300 ctgaaatatg tttgttgctc ttctgacaac aaaggtggtg gttctctgtt ctccgaggat 360 tatactgaaa ctcactacgc tagcgatggc cgtgagatca cgacctctc gtctgttcag 420 ggcggtggta gcaaaatccg tgtgtatgaa atgattaacg cggtgaacac gaaattccgt 480 ccgctgaaaa tccacggtgg cggtggtaaa ctgacgtgca aagcagacaa cgatgaatgc 540 gcagcatttg gtggcggtag ccgtatgcgc gtgttcgaca tggttaacta catcaccgtt 600 gtgtacaaag cgctgaacat tcacggtggt ggtagccagg gcactctgac gtgtaaaggt 660 ggtaacaacg cgaaaaaatc ttgtccgact gaaaagggtg gcaacgtgga agaagaagac 720 gaaacgccgg gtggtgatga tccgaactac ggcatggtgg gtggtggtcc aaaatcttct 780 gcagacgttg aggttctgtg ttgtgacacc aacaagggtg gtaaaccgga cattacctgc 840 accggcgcta aaggtagctg cggcaaaaaa agccgtactc cagagaccac cgaaatttgc 900 ggtggtggct ccggtggcac tatcacttgc aacgctgaca acgatgaagg tggtggtgcg 960 gcaacttgtc cggaagcaaa aagccaccac caccaccacc accaccacca ctga 1014 <210> 9 <211> 91 <212> PRT <213> Artificial Sequence <400> 9 Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp Gly Gly Cys Asp 1 5 10 15 Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr Gly Gly Lys Pro 20 25 30 Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly Gly Gly Gly Lys 35 40 45 Leu Thr Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe Gly Gly Ser 50 55 60 Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu Gly Gly Ser Gln 65 70 75 80 Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala 85 90 <210> 10 <211> 127 <212> PRT <213> Artificial Sequence <400> 10 Met Ala Glu Val Gln Leu Gln Ala Ser Gly Gly Gly Leu Val Gln Ala 1 5 10 15 Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser 20 25 30 Asp Leu Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu 35 40 45 Phe Val Ala Ala Val Ser Trp Ser Val Gly Thr Thr Tyr Tyr Ala Asp 50 55 60 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr 65 70 75 80 Val Asp Leu Gln Met Ile Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr 85 90 95 Tyr Cys Ser Ala Thr Tyr Tyr Thr Gly Glu Tyr Tyr Leu Val Gln Ala 100 105 110 Asp Arg Tyr Gln His Trp Gly Gln Val Thr Val Thr Val Ser Ser 115 120 125 <210> 11 <211> 128 <212> PRT <213> Artificial Sequence <400> 11 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 10 15 Ser Leu Pro Leu Ser Ser Cys Ala Ala Ser Arg Asp Thr Tyr Asp Ser 20 25 30 His Cys Met Ser Met Trp Tyr Arg Gln Ala Pro Gly Lys Glu Arg Glu 35 40 45 Phe Val Ser Ser Met Asn Ser Asp Gly Ser Met Thr Tyr Tyr Ala Asp 50 55 60 Pro Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr 65 70 75 80 Leu Tyr Leu Gln Met Asn Ser Leu Lys Ser Glu Asp Ala Ala Leu Tyr 85 90 95 Tyr Cys Lys Thr Arg Arg Thr Ser Ala Val Asn Trip Leu Cys Arg Ala 100 105 110 Ser Gly Ser Asp Tyr Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser 115 120 125 <210> 12 <211> 381 <212> DNA <213> Private Sequence(Artificial Sequence) <400> 12 atggccgaag tgcaactgca agcttctggt ggaggtcttg tacaagccgg aggatctttg agactgagtt gtgcagccag tggccggact ttctccgatc tgagtatggg atggttcagg 120 caggcaccag gcaaggaag agagttcgtc gccgccgtta gttggagcgt tggcaccact 180 tactacgccg acagcgtga aggccgcttt accatctca gggatacgc caaaaacacc gtcgatctgc buy tctcaaacct gaggacacgg ctgtgtacta ctgttcagcc acatactata caggcgagta ctatctggtg caggctgata ggtatcagca ttggggccaa gtgaccgtga ctgtgagcag t <210> 13 <211> 384 <212> DNA <213> Private Sequence(Artificial Sequence) <400> 13 caggttcagc tggttgaaag tgggggcgga cttgttaaac caggtggctc tctgccattg 60 tcaagctgtg ccgcctctcg ggacacttac gacagtcatt gtatgtcaat gtggtatagg 120 caagccccag gtaaagaaag ggagtttgtc tccagtatga actcagacgg gagcatgacc 180 tactacgctg atcctgtgaa gggcaggttt accattagta gagacaacgc taagaacact 240 ctgtatctgc agatgaattc actgaagagc gaggatgccg ccctgtacta ctgtaagacc 300 cgcagaacca gcgcggtgaa ttggctttgt agagccagcg gttccgacta ttggggacaa 360 ggtacgatgg tgaccgtgtc ctcc 384 <210> 14 <211> 12 <212> PRT <213> Artificial Sequence <400> 14 Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp 1 5 10 <210> 15 <211> 14 <212> PRT <213> Artificial Sequence <400> 15 Cys Asp Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr 1 5 10 <210> 16 <211> 14 <212> PRT <213> Artificial Sequence <400> 16 Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly 1 5 10 <210> 17 <211> 15 <212> PRT <213> Artificial Sequence <400> 17 Gly Lys Leu Thr Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe 1 5 10 15 <210> 18 <211> 13 <212> PRT <213> Artificial Sequence <400> 18 Ser Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu 1 5 10 <210> 19 <211> 13 <212> PRT <213> Artificial Sequence <400> 19 Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala 1 5 10 <210> 20 <211> 27 <212> PRT <213> Artificial Sequence <400> 20 Val Val Tyr Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln 1 5 10 15 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr 20 25 <210> twenty one <211> 25 <212> PRT <213> Artificial Sequence <400> twenty one Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Ser Asp Gly Arg 1 5 10 15 Glu Ile Thr Thr Ser Pro Ser Val Gln 20 25 <210> twenty two <211> 9 <212> PRT <213> Artificial Sequence <400> twenty two Asn Val Glu Glu Glu Asp Glu Thr Pro 1 5 <210> twenty three <211> 8 <212> PRT <213> Artificial Sequence <400> twenty three Thr Trp Glu Ser Asp Glu Pro Phe 1 5 <210> twenty four <211> 7 <212> PRT <213> Artificial Sequence <400> twenty four Asp Cys Gly Ser Pro Arg Asp 1 5 <210> 25 <211> 8 <212> PRT <213> Artificial Sequence <400> 25 Asp Asp Pro Asn Tyr Gly Met Val 1 5 <210> 26 <211> twenty one <212> PRT <213> Artificial Sequence <400> 26 Lys Ile Arg Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg 1 5 10 15 Pro Leu Lys Ile His 20 <210> 27 <211> twenty one <212> PRT <213> Artificial Sequence <400> 27 Arg Met Arg Val Phe Asp Met Val Asn Tyr Ile Thr Val Val Tyr Lys 1 5 10 15 Ala Leu Asn Ile His 20 <210> 28 <211> 5 <212> PRT <213> Artificial Sequence <400> 28 Gln Thr Cys Glu Pro 1 5 <210> 29 <211> 6 <212> PRT <213> Artificial Sequence <400> 29 Ser Cys Pro Thr Glu Lys 1 5 <210> 30 <211> 10 <212> PRT <213> Artificial Sequence <400> 30 Ser Arg Thr Pro Glu Thr Thr Glu Ile Cys 1 5 10 <210> 31 <211> 5 <212> PRT <213> Artificial Sequence <400> 31 Glu Leu Arg Pro Thr 1 5 <210> 32 <211> 9 <212> PRT <213> Artificial Sequence <400> 32 Ala Ala Thr Cys Pro Glu Ala Lys Ser 1 5 <210> 33 <211> 17 <212> PRT <213> Artificial Sequence <400> 33 Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Ser Asp Asn 1 5 10 15 Lys <210> 34 <211> 16 <212> PRT <213> Artificial Sequence <400> 34 Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn Lys 1 5 10 15 <210> 35 <211> 5 <212> PRT <213> Artificial Sequence <400> 35 Asn Ile Pro Pro Gln 1 5 <210> 36 <211> 315 <212> PRT <213> Artificial Sequence <400> 36 Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp Gly Gly Cys Asp 1 5 10 15 Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr Gly Gly Lys Pro 20 25 30 Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly Gly Gly Gly Lys 35 40 45 Leu Thr Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe Gly Gly Ser 50 55 60 Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu Gly Gly Ser Gln 65 70 75 80 Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Gly Gly Val Val Tyr 85 90 95 Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln Asn Pro Gln 100 105 110 Pro Glu Thr Lys Tyr Glu Asp Thr Gly Gly Leu Phe Ser Glu Asp Tyr 115 120 125 Thr Glu Thr His Tyr Ala Ser Asp Gly Arg Glu Ile Thr Thr Ser Pro 130 135 140 Ser Val Gln Gly Gly Asn Val Glu Glu Glu Asp Glu Thr Pro Gly Gly 145 150 155 160 Thr Trp Glu Ser Asp Glu Pro Phe Gly Gly Asp Cys Gly Ser Pro Arg 165 170 175 Asp Gly Gly Asp Asp Pro Asn Tyr Gly Met Val Gly Gly Lys Ile Arg 180 185 190 Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg Pro Leu Lys 195 200 205 Ile His Gly Gly Arg Met Arg Val Phe Asp Met Val Asn Tyr Ile Thr 210 215 220 Val Val Tyr Lys Ala Leu Asn Ile His Gly Gly Gln Thr Cys Glu Pro 225 230 235 240 Gly Gly Ser Cys Pro Thr Glu Lys Gly Gly Ser Arg Thr Pro Glu Thr 245 250 255 Thr Glu Ile Cys Gly Gly Glu Leu Arg Pro Thr Gly Gly Ala Ala Thr 260 265 270 Cys Pro Glu Ala Lys Ser Gly Gly Pro Lys Asn Ser Ala Leu Leu Lys 275 280 285 Tyr Val Cys Cys Ser Ser Asp Asn Lys Gly Gly Pro Lys Ser Ser Ala 290 295 300 Asp Val Glu Val Leu Cys Cys Asp Thr Asn Lys 305 310 315 <210> 37 <211> 314 <212> PRT <213> Artificial Sequence <400> 37 Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp Gly Gly Val Val 1 5 10 15 Tyr Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln Asn Pro 20 25 30 Gln Pro Glu Thr Lys Tyr Glu Asp Thr Gly Gly Gln Thr Cys Glu Pro 35 40 45 Gly Gly Cys Asp Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr 50 55 60 Gly Gly Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Ser Asp 65 70 75 80 Gly Arg Glu Ile Thr Thr Ser Pro Ser Val Gln Gly Gly Ser Cys Pro 85 90 95 Thr Glu Lys Gly Gly Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly 100 105 110 Ser Cys Gly Gly Gly Asn Val Glu Glu Glu Asp Glu Thr Pro Gly Gly 115 120 125 Ser Arg Thr Pro Glu Thr Thr Glu Ile Cys Gly Gly Gly Lys Leu Thr 130 135 140 Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe Gly Gly Thr Trp Glu 145 150 155 160 Ser Asp Glu Pro Phe Gly Gly Glu Leu Arg Pro Thr Gly Gly Ser Gly 165 170 175 Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu Gly Gly Asp Cys Gly 180 185 190 Ser Pro Arg Asp Gly Gly Ala Ala Thr Cys Pro Glu Ala Lys Ser Gly 195 200 205 Gly Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Gly Gly 210 215 220 Asp Asp Pro Asn Tyr Gly Met Val Gly Gly Pro Lys Asn Ser Ala Leu 225 230 235 240 Leu Lys Tyr Val Cys Cys Ser Ser Asp Asn Lys Gly Gly Pro Lys Ser 245 250 255 Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn Lys Gly Gly Lys 260 265 270 Ile Arg Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg Pro 275 280 285 Leu Lys Ile His Gly Gly Arg Met Arg Val Phe Asp Met Val Asn Tyr 290 295 300 Ile Thr Val Val Tyr Lys Ala Leu Asn Ile 305 310 <210> 38 <211> 315 <212> PRT <213> Artificial Sequence <400> 38 Gln Thr Cys Glu Pro Gly Gly Glu Leu Arg Pro Thr Gly Gly Ser Cys 1 5 10 15 Pro Thr Glu Lys Gly Gly Asp Cys Gly Ser Pro Arg Asp Gly Gly Thr 20 25 30 Trp Glu Ser Asp Glu Pro Phe Gly Gly Asp Asp Pro Asn Tyr Gly Met 35 40 45 Val Gly Gly Asn Val Glu Glu Glu Asp Glu Thr Pro Gly Gly Ala Ala 50 55 60 Thr Cys Pro Glu Ala Lys Ser Gly Gly Ser Arg Thr Pro Glu Thr Thr 65 70 75 80 Glu Ile Cys Gly Gly Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu 85 90 95 Asp Gly Gly Ser Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu 100 105 110 Gly Gly Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Gly 115 120 125 Gly Cys Asp Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr Gly 130 135 140 Gly Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly Gly 145 150 155 160 Gly Gly Lys Leu Thr Cys Lys Ala Asp Asn Asp Glu Cys Ala Ala Phe 165 170 175 Gly Gly Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr 180 185 190 Asn Lys Gly Gly Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys 195 200 205 Ser Ser Asp Asn Lys Gly Gly Arg Met Arg Val Phe Asp Met Val Asn 210 215 220 Tyr Ile Thr Val Val Tyr Lys Ala Leu Asn Ile His Gly Gly Lys Ile 225 230 235 240 Arg Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg Pro Leu 245 250 255 Lys Ile His Gly Gly Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr 260 265 270 Ala Ser Asp Gly Arg Glu Ile Thr Thr Ser Pro Ser Val Gln Gly Gly 275 280 285 Val Val Tyr Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln 290 295 300 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr 305 310 315 <210> 39 <211> 328 <212> PRT <213> Artificial Sequence <400> 39 Gln Thr Cys Glu Pro Gly Gly Glu Leu Arg Pro Thr Lys Lys Cys Asp 1 5 10 15 Arg Ala Ala Ala Ile Cys Phe Ala Ala Ala Pro Tyr Lys Lys Tyr Cys 20 25 30 Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp Gly Gly Gly Thr Trp Glu 35 40 45 Ser Asp Glu Pro Phe Gly Gly Asp Cys Gly Ser Pro Arg Asp Lys Lys 50 55 60 Val Val Tyr Pro Gln Lys Val Pro Ser Leu Pro Lys Gly Gly Val Gln 65 70 75 80 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr Gly Gly Gly Pro Lys 85 90 95 Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Ser Asp Asn Lys Gly 100 105 110 Gly Gly Ser Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Ser 115 120 125 Asp Gly Arg Glu Ile Thr Thr Ser Pro Ser Val Gln Gly Gly Gly Ser 130 135 140 Lys Ile Arg Val Tyr Glu Met Ile Asn Ala Val Asn Thr Lys Phe Arg 145 150 155 160 Pro Leu Lys Ile His Gly Gly Gly Gly Lys Leu Thr Cys Lys Ala Asp 165 170 175 Asn Asp Glu Cys Ala Ala Phe Gly Gly Gly Ser Arg Met Arg Val Phe 180 185 190 Asp Met Val Asn Tyr Ile Thr Val Val Tyr Lys Ala Leu Asn Ile His 195 200 205 Gly Gly Gly Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala 210 215 220 Lys Lys Ser Cys Pro Thr Glu Lys Gly Gly Asn Val Glu Glu Glu Asp 225 230 235 240 Glu Thr Pro Gly Gly Asp Asp Pro Asn Tyr Gly Met Val Gly Gly Gly [[ID=十六]]245 250 255[[ID=十七]] [[ID=十八]]Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn Lys[[ID=十九]] [[ID=二十]]26十五 270[[ID=二十一]] [[ID=二十二]]Gly Gly Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly[[ID=二十三]] [[ID=二十四]]275 280 285[[ID=二十五]] [[ID=二十六]]Lys Lys Ser Arg Thr Pro Glu Thr Thr Glu Ile Cys Gly Gly Gly Ser[[ID=二十七]] [[ID=二十八]]290 295 300[[ID=二十九]] [[ID=三十]]Gly Gly Thr Ile Thr Cys Asn Ala Asp Asn Asp Glu Gly Gly Gly Ala[[ID=三十一]] [[ID=三十二]]305 310 315 320[[ID=三十三]] [[ID=三十四]]Ala Thr Cys Pro Glu Ala Lys Ser[[ID=三十五]] [[ID=三十六]]325[[ID=三十七]] [[ID=三十八]]<210> 40[[ID=三十九]] [[ID=四十]]<211> 945[[ID=四十一]] [[ID=四十二]]<212> DNA[[ID=四十三]] [[ID=四十四]]<213> Artificial Sequence[[ID=四十五]] It should be noted that there may be some inaccuracies in the above translation due to the lack of clear context for the Chinese text in the original. It is recommended to double-check with the original text and relevant background information for more accurate translation.<400> 40 tattgtggtc ctggtggtac tggtactcca ctggatggtg gttgtgatcg tgcagctgcc 60 atttgtttcg ctgcagcgcc gtatggtggt aaaccggaca ttacctgtac tggtgccaaa 120 ggtagctgtg gtggcggtgg caaactgacc tgtaaagcag ataatgatga atgcgctgct 180 ttcggtggct ctggtggcac catcacctgc aacgcggata acgatgaagg cggttctcag 240 ggcaccctga cttgcaaagg tggcaacaac gcgggtggcg tcgtttaccc gcagaaagtt 300 ccatccctgc cgaaaggcgg cgtgcaaaac ccgcagccag aaaccaaata cgaggacacc 360 ggcggtctgt tttccgaaga ctataccgaa acccattacg ctagcgacgg ccgtgagatt 420 actacttctc cgagcgtaca gggtggcaac gttgaagagg aagatgagac cccgggcggt 480 acttgggaaa gcgacgaacc gtttggtggt gattgcggct ctccgcgtga tggcggtgat 540 gatccgaact acggcatggt tggtggcaag atccgtgtgt acgaaatgat caacgcggtg 600 aacaccaaat tccgtccact gaaaatccac ggtggccgta tgcgtgtgtt cgacatggtg 660 aactacatca ccgtagttta taaagcgctg aacatccacg gcggccagac ttgcgaacca 720 ggtggtagct gcccgactga gaaaggcggt tctcgtaccc cggaaacgac tgaaatttgt 780 ggtggtgaac tgcgtccgac tggtggtgca gcaacctgtc cggaagctaa atctggcggt 840 ccgaagaact ccgcgctgct gaaatatgtt tgctgctcct ccgataacaa aggtggcccg 900 aaatcttctg cagatgtcga agttctgtgc tgtgatacca ataag 945 <210> 41 <211> 942 <212> DNA <213> Artificial Sequence <400> 41 tattgcggtc ctggtggtac tggtactcca ctggatggtg gtgttgtta tccgcagaaaa 60 gttccgtctc tgccaaaggg tggcgttcag aacccgcagc ctgaaaccaa atacgaagat 120 acgggcggtc agacctgtga accgggtggt tgcgatcgtg cggctgctat ctgttttgcc 180 gcagcgccgt atggtggtct gttttctgaa gattacaccg aaacccacta cgcttctgac 240 ggtcgtgaaa tcaccacttc cccttctgtg cagggtggct cttgcccaac tgagaaaggt 300 ggcaaaccgg acattacctg taccggtgcc aaaggttcct gcggtggtgg caatgtagaa 360 gaggaagacg aaaccccggg tggttctcgt accccggaga ctaccgaaat ttgcggtggt 420 ggcaaactga cctgtaaagc cgataacgac gaatgcgcag cttttggcgg cacctgggaa 480 agcgatgaac cttttggtgg cgaactgcgt ccgactggtg gttccggtgg cactatcacc 540 tgcaacgcgg acaacgacga aggcggtgat tgtggttctc cgcgtgatgg cggtgctgca 600 acctgtccag aagcaaagtc tggtggcagc cagggtaccc tgacctgtaa aggtggcaat 660 aacgctggcg gcgatgaccc aaactatggt atggtaggtg gtcctaaaaa ctccgctctg 720 ctgaaatacg tgtgctgcag ctctgataac aaaggtggtc cgaagtctag cgctgatgtc 780 gaagttctgt gctgcgacac taacaaaggc ggcaaaatcc gtgtttacga aatgattaac 840 gcagttaaca ctaaattccg tccgctgaaa atccacggtg gtcgtatgcg tgttttcgac 900 atggttaact acatcacggt agtgtataaa gctctgaaca tc 942 <210> 42 <211> 941 <212> DNA <213> Artificial Sequence <400> 42 caaacttgtg aaccgggtgg tgaactgcgt ccaactggtg gttcttgtcc gacggaaaaa 60 ggtggcgatt gcggttctcc gcgtgatggt ggcacttggg aaagcgatga accgttcggt 120 ggtgacgatc cgaactacgg tatggtgggt ggtaacgttg aagaagaaga tgaaactcct 180 ggtggtgcag cgacttgtcc ggaagcgaaa agcggtggta gccgtactcc tgaaaccacc 240 gaaatttgtg gcggttattg tggtccaggc ggtaccggta cccctctgga tggtggtagc 300 ggcggtacta ttacctgcaa cgcagacaac gacgaaggcg gttctcaggg tactctgacc 360 tgtaaaggtg gtaacaacgc gggtggttgc gatcgtgctg ctgccatttg cttcgctgca 420 gcaccgtatg gcggtaaacc ggatatcacc tgcaccggcg ctaaaggttc ttgcggtggt 480 ggcggtaaac tgacttgtaa agcggataac gatgagtgtg cagcctttgg tggcccgaaa 540 agctccgcgg acgttgaagt tctgtgctgt gataccaaca aaggtggtcc gaaaaacagc 600 gcactgctga aatatgtttg ttgttcttcc gacaacaaag gcggtcgtat gcgtgtgttc 660 gatatggtta actacatcac cgtggtttac aaggcgctga acattcacgg cggtaagatc 720 cgtgtttacg aaatgatcaa cgctgttaac actaaattcc gcccgctgaa aatccacggt 780 ggtctgttct ccgaggacta tactgaaacc cattacgcgt ctgacggccg tgaaatcacc 840 accagcccgt ccgttcaggg tggtgttgta tacccacaga aagttccgtc tctgccgaag 900 ggtggtgtgc aaaacccgca gccagaaacc aaatacgaag a 941 <210> 43 <211> 984 <212> DNA <213> Artificial Sequence <400> 43 cagacttgtg aacctggtgg cgaactgcgt ccgaccaaaa agtgtgatcg tgctgcagca 60 atttgtttcg cggctgcgcc gtataagaaa tactgtggtc cgggtggtac cggtactcct 120 ctggatggtg gtggtacctg ggaaagcgat gaaccattcg gcggtgactg tggttctccg 180 cgtgacaaaa aagttgtgta tcctcagaaa gttccgagcc tgcctaaggg cggtgttcag 240 aacccgcagc ctgaaacgaa atacgaagat actggtggtg gtccgaaaaa ctctgcgctg 300 ctgaaatatg tttgttgctc ttctgacaac aaaggtggtg gttctctgtt ctccgaggat 360 tatactgaaa ctcactacgc tagcgatggc cgtgagatca cgacctctcc gtctgttcag 420 ggcggtggta gcaaaatccg tgtgtatgaa atgattaacg cggtgaacac gaaattccgt 480 ccgctgaaaa tccacggtgg cggtggtaaa ctgacgtgca aagcagacaa cgatgaatgc gcagcatttg gtggcggtag ccgtatgcgc gtgttcgaca tggttaacta catcaccgtt 600 660. gtgtacaaag cgctgaacat tcacggtggt ggtagccagg gcactctgac gtgtaaaggt ggtaacaacg cgaaaaaatc ttgtccgact gaaagggtg gcaacgtgga agaagaagac gaaacgccgg gtggtgatga tccgaactac ggcatggtgg gtggtggtcc aaaatcttct 780 gcagacgttg aggttctgtg ttgtgacacc aacaagggtg gtaaaccgga cattacctgc 840 accggcgcta aaggtagctg cggcaaaaaa agccgtactc cagagaccac cgaaatttgc ggtggtggct ccggtggcac tatcacttgc aacgctgaca acgatgaagg tggtggtgcg gcaacttgtc cggaagcaaa aagc 984 <210> 44 <211> 8 <212> PRT <213> Private Sequence(Artificial Sequence) <400> 44 God God Ser Gly Arg Thr Phe Ser 1 5 <210> 45 <211> 8 <212> PRT <213> Private Sequence(Artificial Sequence) <400> 45 Ala Val Ser Trp Ser Val Gly Thr 1 5 <210> 46 <211> 19 <212> PRT <213> Artificial Sequence <400> 46 Ser Ala Thr Tyr Tyr Thr Gly Glu Tyr Tyr Leu Val Gln Ala Asp Arg 1 5 10 15 Tyr Gln His <210> 47 <211> 8 <212> PRT <213> Artificial Sequence <400> 47 Arg Asp Thr Tyr Asp Ser His Cys 1 5 <210> 48 <211> 8 <212> PRT <213> Artificial Sequence <400> 48 Met Asn Ser Asp Gly Ser Met Thr 1 5 <210> 49 <211> 19 <212> PRT <213> Artificial Sequence <400> 49 Lys Thr Arg Arg Thr Ser Ala Val Asn Trp Leu Cys Arg Ala Ser Gly 1 5 10 15 Ser Asp Tyr <210> 50 <211> 135 <212> PRT <213> Banded krait <400> 50 Ala Val Cys Val Ser Leu Leu Gly Ala Ala Asn Ile Pro Pro Gln Ser 1 5 10 15 Leu Asn Leu Tyr Gln Phe Lys Asn Met Ile Glu Cys Ala Gly Thr Arg 20 25 30 Thr Trp Leu Ala Tyr Val Lys Tyr Gly Cys Tyr Cys Gly Pro Gly Gly 35 40 45 Thr Gly Thr Pro Leu Asp Glu Leu Asp Arg Cys Cys Gln Thr His Asp 50 55 60 His Cys Tyr Asp Asn Ala Lys Lys Phe Gly Asn Cys Ile Pro Tyr Leu 65 70 75 80 Lys Thr Tyr Val Tyr Thr Cys Asn Lys Pro Asp Ile Thr Cys Thr Gly 85 90 95 Ala Lys Gly Ser Cys Gly Arg Asn Val Cys Asp Cys Asp Arg Ala Ala 100 105 110 Ala Ile Cys Phe Ala Ala Ala Pro Tyr Asn Leu Ala Asn Phe Gly Ile 115 120 125 Asp Lys Glu Lys His Cys Gln 130 135 <210> 51 <211> 135 <212> PRT <213> Banded krait <400> 51 Ala Val Cys Val Ser Leu Leu Gly Ala Ala Asn Ile Pro Pro Gln Pro 1 5 10 15 Leu Asn Leu Leu Gln Phe Lys Asn Met Ile Gln Cys Ala Gly Ser Arg 20 25 30 Leu Trp Val Ala Tyr Val Lys Tyr Gly Cys Tyr Cys Gly Pro Gly Gly 35 40 45 Thr Gly Thr Pro Leu Asp Gln Leu Asp Arg Cys Cys Gln Thr His Asp 50 55 60 His Cys Tyr Asp Asn Ala Lys Lys Phe Gly Asn Cys Ile Pro Tyr Phe 65 70 75 80 Lys Ser Tyr Glu Tyr Thr Cys Asn Lys Pro Asp Leu Thr Cys Thr Asp 85 90 95 Ala Lys Gly Ser Cys Ala Arg Asn Val Cys Asp Cys Asp Arg Ala Ala 100 105 110 Ala Ile Cys Phe Ala Ala Ala Pro Tyr Asn Leu Ala Asn Phe Gly Ile 115 120 125 Asn Lys Glu Thr His Cys Gln 130 135 <210> 52 <211> 145 <212> PRT <213> Banded krait <400> 52 Met Asn Pro Ala His Leu Leu Val Leu Leu Ala Val Cys Val Ser Leu 1 5 10 15 Leu Ala Ala Ala Asn Ile Pro Pro Gln Ser Leu Asn Leu Leu Gln Phe 20 25 30 Lys Asn Met Ile Glu Cys Ala Gly Thr Arg Thr Trp Met Ala Tyr Val 35 40 45 Lys Tyr Gly Cys Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp 50 55 60 Glu Leu Asp Arg Cys Cys Gln Thr His Asp Gln Cys Tyr Asp Asn Ala 65 70 75 80 Lys Lys Phe Gly Asn Cys Ile Pro Tyr Phe Lys Thr Tyr Val Tyr Thr 85 90 95 Cys Asn Lys Pro Asp Ile Thr Cys Thr Gly Ala Lys Gly Ser Cys Gly 100 105 110 Arg Thr Val Cys Asp Cys Asp Arg Ala Ala Ala Leu Cys Phe Ala Ala 115 120 125 Ala Pro Tyr Asn Leu Ala Asn Phe Gly Ile Asn Lys Glu Thr His Cys 130 135 140 Gln 145 <210> 53 <211> 135 <212> PRT <213> Banded krait <400> 53 Ala Val Cys Val Ser Leu Leu Gly Ala Ala Asn Ile Pro Pro Gln Pro 1 5 10 15 Leu Asn Leu Leu Gln Phe Lys Asn Met Ile Gln Cys Ala Gly Ser Arg 20 25 30 Leu Trp Val Ala Tyr Val Lys Tyr Gly Cys Tyr Cys Gly Pro Gly Gly 35 40 45 Thr Gly Thr Pro Leu Asp Gln Leu Asp Arg Cys Cys Gln Thr His Asp 50 55 60 His Cys Tyr Asp Asn Ala Lys Lys Phe Gly Asn Cys Ile Pro Tyr Phe 65 70 75 80 Lys Thr Tyr Glu Tyr Thr Cys Asn Lys Pro Asp Ile Thr Cys Thr Asp 85 90 95 Ala Lys Gly Ser Cys Gly Arg Thr Val Cys Asp Cys Asp Arg Ala Ala 100 105 110 Ala Ile Cys Phe Ala Ala Ala Pro Tyr Asn Leu Ala Asn Phe Gly Ile 115 120 125 Asp Lys Glu Lys His Cys Gln 130 135 <210> 54 <211> 145 <212> PRT <213> Banded krait <400> 54 Met Asn Pro Ala His Leu Leu Val Leu Leu Ala Val Cys Val Ser Leu 1 5 10 15 Leu Gly Ala Ala Asn Ile Pro Pro Gln Ser Leu Asn Leu Tyr Gln Phe 20 25 30 Lys Asn Met Ile Gln Cys Ala Gly Thr Gln Leu Cys Val Ala Tyr Val 35 40 45 Lys Tyr Gly Cys Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp 50 55 60 Gln Leu Asp Arg Cys Cys Gln Thr His Asp His Cys Tyr Asp Asn Ala 65 70 75 80 Lys Lys Phe Gly Asn Cys Ile Pro Tyr Phe Lys Thr Tyr Glu Tyr Thr 85 90 95 Cys Asn Lys Pro Asp Leu Thr Cys Thr Asp Ala Lys Gly Ser Cys Ala 100 105 110 Arg Asn Val Cys Asp Cys Asp Arg Ala Ala Ala Ile Cys Phe Ala Ala 115 120 125 Ala Pro Tyr Asn Leu Ala Asn Phe Gly Ile Asn Lys Glu Thr His Cys 130 135 140 Gln 145 <210> 55 <211> 135 <212> PRT <213> Banded krait <400> 55 Ala Val Cys Val Ser Leu Leu Gly Ala Ala Asn Ile Pro Pro Gln Pro 1 5 10 15 Leu Asn Leu Tyr Gln Phe Lys Asn Met Ile Gln Cys Ala Gly Thr Gln 20 25 30 Leu Trp Val Ala Tyr Val Asn Tyr Gly Cys Tyr Cys Gly Lys Gly Gly 35 40 45 Ser Gly Thr Pro Val Asp Gln Leu Asp Arg Cys Cys Gln Thr His Asp 50 55 60 His Cys Tyr His Asn Ala Lys Arg Phe Gly Lys Cys Asn Pro Tyr Phe 65 70 75 80 Lys Thr Tyr Glu Tyr Thr Cys Asn Lys Pro Asn Leu Thr Cys Arg Gly 85 90 95 Ala Lys Gly Ser Cys Gly Arg Asn Val Cys Asp Cys Asp Arg Ala Ala 100 105 110 Ala Ile Cys Phe Ala Ala Ala Pro Tyr Asn Leu Ser Asn Phe Gly Ile 115 120 125 Asn Lys Lys Thr His Cys Lys 130 135 <210> 56 <211> 120 <212> PRT <213> Banded krait <400> 56 Asn Leu Phe Gln Phe Lys Asn Met Ile Gln Cys Ala Gly Thr Arg Ser 1 5 10 15 Trp Thr Asp Tyr Val Ser Tyr Gly Cys Tyr Cys Gly Lys Gly Gly Ser 20 25 30 Gly Thr Pro Val Asp Gln Leu Asp Arg Cys Cys Lys Val His Asp Asp 35 40 45 Cys Tyr Gly Asp Ala Glu Lys Ile Pro Lys Cys Lys Pro Tyr Tyr Lys 50 55 60 Thr Tyr Ser Tyr Asp Cys Ser Glu Gly Lys Leu Thr Cys Lys Ala Asp 65 70 75 80 Asn Asp Glu Cys Ala Ala Phe Ile Cys Asn Cys Asp Arg Val Ala Ala 85 90 95 Ile Cys Phe Ala Gly Ala Pro Tyr Asn Asp Asn Asn Phe Met Ile Asp 100 105 110 Ser Lys Thr Arg Cys Asn Asp Ile 115 120 <210> 57 <211> 142 <212> PRT <213> Banded krait <400> 57 Ala Val Cys Val Ser Leu Leu Gly Ala Ser Ile Ile Pro Pro Gln Pro 1 5 10 15 Leu Asp Leu Leu Gln Phe Asn Glu Met Ile Glu Cys Thr Ile Pro Gly 20 25 30 Ser Phe Pro Leu Leu Asp Tyr Met Asp Tyr Gly Cys Tyr Cys Gly Thr 35 40 45 Gly Gly Arg Gly Thr Pro Val Asp Ala Leu Asp Arg Cys Cys Lys Glu 50 55 60 His Asp Asp Cys Tyr Ala Gln Ile Lys Glu Asn Pro Lys Cys Ser Ser 65 70 75 80 Leu Leu Asn Val Pro Tyr Val Lys Gln Tyr Ser Tyr Thr Cys Ser Glu 85 90 95 Gly Asn Leu Thr Cys Ser Ala Asp Asn Asp Glu Cys Ala Ala Phe Ile 100 105 110 Cys Asn Cys Asp Arg Thr Ala Ala Leu Cys Phe Ala Glu Val Pro Tyr 115 120 125 Lys Arg Arg Asn Phe Arg Ile Asp Tyr Lys Ser Arg Cys Gln 130 135 140 <210> 58 <211> 145 <212> PRT <213> Banded krait <400> 58 Met Asn Pro Ala His Leu Leu Val Leu Leu Ala Val Cys Val Ser Leu 1 5 10 15 Leu Gly Ala Ala Asn Ile Pro Pro Gln Pro Leu Asn Leu Leu Gln Phe 20 25 30 Lys Asn Met Ile Gln Cys Ala Gly Ser Arg Leu Trp Val Ala Tyr Val 35 40 45 Lys Tyr Gly Cys Tyr Cys Gly Pro Gly Gly Thr Gly Thr Pro Leu Asp 50 55 60 Gln Leu Asp Arg Cys Cys Gln Thr His Asp His Cys Tyr Asp Asn Ala 65 70 75 80 Lys Lys Phe Gly Asn Cys Ile Pro Tyr Phe Lys Thr Tyr Glu Tyr Thr 85 90 95 Cys Asn Lys Pro Asp Leu Thr Cys Thr Asp Ala Lys Gly Ser Cys Ala 100 105 110 Arg Asn Val Cys Asp Cys Asp Arg Ala Ala Ala Ile Cys Phe Ala Ala 115 120 125 Ala Pro Tyr Asn Leu Ala Asn Phe Gly Ile Asn Lys Glu Thr His Cys 130 135 140 Gln 145 <210> 59 <211> 118 <212> PRT <213> Banded krait <400> 59 Asn Met Val Gln Phe Lys Ser Met Val Gln Cys Thr Ser Thr Arg Pro 1 5 10 15 Trp Leu Asp Tyr Val Asp Tyr Gly Cys Asn Cys Asp Ile Gly Gly Thr 20 25 30 Gly Thr Pro Leu Asp Glu Leu Asp Arg Cys Cys Gln Thr His Ala Asn 35 40 45 Cys Tyr Thr Glu Ala Arg Lys Phe Pro Glu Cys Ala Pro Tyr Tyr Lys 50 55 60 Thr Tyr Ser Tyr Thr Cys Ser Gly Gly Thr Ile Thr Cys Asn Ala Asp 65 70 75 80 Asn Asp Glu Cys Ala Ala Ser Val Cys Asn Cys Asp Arg Thr Ala Ala 85 90 95 Leu Cys Phe Ala Gly Ala Pro Tyr Asn Gln Asn Asn Phe Asp Val Asp 100 105 110 Leu Glu Thr Arg Cys Gln 115 <210> 60 <211> 146 <212> PRT <213> Chinese cobra <400> 60 Met Thr Pro Ala His Leu Leu Ile Leu Ala Ala Val Cys Val Ser Pro 1 5 10 15 Leu Gly Ala Ser Ser Asn Arg Pro Met Pro Leu Asn Leu Tyr Gln Phe 20 25 30 Lys Asn Met Ile Gln Cys Thr Val Pro Ser Arg Ser Trp Trp Asp Phe 35 40 45 Ala Asp Tyr Gly Cys Tyr Cys Gly Arg Gly Gly Ser Gly Thr Pro Val 50 55 60 Asp Asp Leu Asp Arg Cys Cys Gln Val His Asp Asn Cys Tyr Asn Glu 65 70 75 80 Ala Glu Lys Ile Ser Gly Cys Trp Pro Tyr Phe Lys Thr Tyr Ser Tyr 85 90 95 Glu Cys Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Cys 100 105 110 Ala Ala Ala Val Cys Asp Cys Asp Arg Leu Ala Ala Ile Cys Phe Ala 115 120 125 Gly Ala Pro Tyr Asn Asn Asn Asn Tyr Asn Ile Asp Leu Lys Ala Arg 130 135 140 Cys Gln 145 <210> 61 <211> 119 <212> PRT <213> Chinese cobra <400> 61 Asn Leu Tyr Gln Phe Lys Asn Met Ile Gln Cys Thr Val Pro Ser Arg 1 5 10 15 Ser Trp Trp Asp Phe Ala Asp Tyr Gly Cys Tyr Cys Gly Lys Gly Gly 20 25 30 Ser Gly Thr Pro Val Asp Asp Leu Asp Arg Cys Cys Gln Val His Asp 35 40 45 Asn Cys Tyr Asn Glu Ala Glu Lys Ile Ser Gly Cys Trp Pro Tyr Phe 50 55 60 Lys Thr Tyr Ser Tyr Glu Cys Ser Gln Gly Thr Leu Thr Cys Lys Gly 65 70 75 80 Gly Asn Asn Ala Cys Ala Ala Ala Val Cys Asp Cys Asp Arg Leu Ala 85 90 95 Ala Ile Cys Phe Ala Gly Ala Pro Tyr Thr Asp Ala Asn Tyr Asn Ile 100 105 110 Asp Leu Lys Ala Arg Cys Gln 115 <210> 62 <211> 146 <212> PRT <213> Chinese cobra <400> 62 Met Thr Pro Ala His Leu Leu Ile Leu Ala Ala Val Cys Val Ser Pro 1 5 10 15 Leu Gly Ala Ser Ser Ser Arg Pro Met Pro Leu Asn Leu Tyr Gln Phe 20 25 30 Lys Asn Met Ile Gln Cys Thr Val Pro Ser Arg Ser Trp Trp Asp Phe 35 40 45 Ala Asp Tyr Gly Cys Tyr Cys Gly Arg Gly Gly Ser Gly Thr Pro Val 50 55 60 Asp Asp Leu Asp Arg Cys Cys Gln Val His Asp His Cys Tyr Asn Glu 65 70 75 80 Ala Glu Lys Ile Ser Gly Cys Trp Pro Tyr Ser Lys Thr Tyr Ser Tyr 85 90 95 Glu Cys Ser Gln Gly Thr Leu Thr Cys Lys Gly Gly Asn Asn Ala Cys 100 105 110 Ala Ala Ala Val Cys Asp Cys Asp Arg Leu Ala Ala Ile Cys Phe Ala 115 120 125 Gly Ala Pro Tyr Asn Asn Asn Asn Tyr Asn Ile Asp Leu Lys Ala Arg 130 135 140 Cys Gln 145 <210> 63 <211> 151 <212> PRT <213> King cobra <400> 63 Met Asn Pro Ala His Leu Leu Val Leu Ser Ala Val Cys Val Ser Leu 1 5 10 15 Leu Gly Ala Ser Ser Ile Pro Pro Gln Pro Leu His Leu Ile Gln Phe 20 25 30 Gly Asn Met Ile Gln Cys Thr Val Pro Gly Phe Leu Ser Trp Ile Lys 35 40 45 Tyr Ala Asp Tyr Gly Cys Tyr Cys Gly Ala Gly Gly Ser Gly Thr Pro 50 55 60 Val Asp Lys Leu Asp Arg Cys Cys Gln Val His Asp Asn Cys Tyr Thr 65 70 75 80 Gln Ala Gln Lys Leu Pro Ala Cys Ser Ser Ile Met Asp Ser Pro Tyr 85 90 95 Val Lys Ile Tyr Ser Tyr Asp Cys Ser Glu Arg Thr Val Thr Cys Lys 100 105 110 Ala Asp Asn Asp Glu Cys Ala Ala Phe Ile Cys Asn Cys Asp Arg Val 115 120 125 Ala Ala His Cys Phe Ala Ala Ser Pro Tyr Asn Asn Asn Asn Tyr Asn 130 135 140 Ile Asp Thr Thr Thr Arg Cys 145 150 <210> 64 <211> 146 <212> PRT <213> King cobra <400> 64 Met Asn Pro Ala His Leu Leu Val Leu Ser Ala Val Cys Val Ser Leu 1 5 10 15 Leu Gly Ala Ser Ser Ile Pro Pro Gln Pro Leu His Leu Val Gln Phe 20 25 30 Asn Gly Met Ile Arg Cys Thr Ile Pro Gly Ser Ile Pro Trp Trp Asp 35 40 45 Tyr Ser Asp Tyr Gly Cys Tyr Cys Gly Ser Gly Gly Ser Gly Thr Pro 50 55 60 Val Asp Glu Leu Asp Arg Cys Cys Gln Val His Asp Asn Cys Tyr Thr 65 70 75 80 Gln Ala Gln Gln Leu Thr Glu Cys Ser Pro Tyr Ser Lys Arg Tyr Ser 85 90 95 Tyr Asp Cys Ser Glu Gly Thr Leu Thr Cys Lys Ala Asp Asn Asp Glu 100 105 110 Cys Ala Ala Phe Val Cys Asp Cys Asp Arg Val Ala Ala Ile Cys Phe 115 120 125 Ala Gly Ala Pro Tyr Asn Lys Glu Asn Ile Asn Ile Asp Thr Thr Thr 130 135 140 Arg Cys 145 <210> 65 <211> 152 <212> PRT <213> King cobra <400> 65 Met Asn Pro Ala His Leu Leu Val Leu Ser Ala Val Cys Val Ser Leu 1 5 10 15 Leu Gly Ala Ser Ser Ile Pro Pro Gln Pro Leu Asn Leu Leu Gln Phe 20 25 30 Asn Tyr Met Ile Gln Cys Thr Ile Pro Gly Ser Arg Pro Phe Leu Asp 35 40 45 Tyr Met Asp Tyr Gly Cys Tyr Cys Gly Thr Gly Val Ala Gly His Pro 50 55 60 Val Asp Glu Leu Asp Arg Cys Cys Gln Thr His Asp Leu Cys Tyr Ser 65 70 75 80 Lys Ala Glu Glu Gln Pro Lys Cys Ser Ser Leu Leu Asn Ser Pro Leu 85 90 95 Met Lys Lys Tyr Ser Tyr Thr Cys Ser Gly Gly Thr Leu Thr Cys Asn 100 105 110 Asp Asp Asn Asp Glu Cys Gly Ala Phe Ile Cys Asn Cys Asp Arg Ala 115 120 125 Ala Arg Ile Cys Phe Ala Gly Ala Pro Tyr Asn Lys Glu Asn Lys Glu 130 135 140 Leu Asp Ile Ala Thr Arg Cys Gln 145 150 <210> 66 <211> 605 <212> PRT <213> Banded krait <400> 66 Met Leu Val Val Phe Pro Tyr Gln Gly Ser Ser Ile Ile Leu Glu Ser 1 5 10 15 Gly Asn Val Asn Asp Tyr Glu Val Val Tyr Pro Gln Lys Val Pro Ser 20 25 30 Leu Pro Lys Gly Gly Val Gln Asn Pro Gln Pro Glu Thr Lys Tyr Glu 35 40 45 Asp Thr Met Gln Tyr Glu Phe His Val Asn Gly Glu Pro Val Val Pro 50 55 60 His Leu Glu Lys Asn Lys Gly Leu Phe Ser Glu Asp Tyr Thr Glu Thr 65 70 75 80 His Tyr Ala Ser Asp Gly Arg Glu Ile Thr Thr Ser Pro Ser Val Gln 85 90 95 Asp His Cys Tyr Tyr Tyr Gly Tyr Ile Gln Asn Glu Ala Asp Ser Ser 100 105 110 Ala Ala Ile Ser Ala Cys Asp Gly Leu Lys Gly His Phe Lys His Gln 115 120 125 Gly Glu Thr Tyr Phe Ile Glu Pro Leu Lys Leu Ser Asn Ser Glu Ala 130 135 140 His Ala Ile Tyr Lys Asp Glu Asn Val Glu Glu Glu Asp Glu Thr Pro 145 150 155 160 Lys Ile Cys Gly Leu Thr Gln Thr Thr Trp Glu Ser Asp Glu Pro Phe 165 170 175 Lys Asn Thr Ser Leu Leu Ile Tyr Thr Pro Glu Gln Asn Arg Tyr Leu 180 185 190 Gln Ala Lys Lys Tyr Ile Glu Phe Tyr Val Ala Val Asp Asn Arg Met 195 200 205 Tyr Arg His Tyr Lys Arg Asn Lys Thr Val Ile Lys Arg Arg Val Tyr 210 215 220 Glu Leu Val Asn Ile Leu Asn Thr Ile Phe Arg Arg Leu Asn Phe Tyr 225 230 235 240 Ile Ala Leu Ile Gly Leu Glu Ile Trp Ser Lys Arg Asp Lys Val Asn 245 250 255 Val Gln Ser Asp Val Lys Val Thr Leu Lys Ser Phe Gly Lys Trp Arg 260 265 270 Glu Lys Lys Val Ala Ala Thr Gln Lys Glu Tyr Asn Ala Gln Leu Leu 275 280 285 Thr Arg Ile Asp Phe Asn Gly Asn Thr Val Gly Leu Ala Ala Leu Gly 290 295 300 Ala Leu Cys Ser Val Lys Tyr Ser Val Ala Val Ile Gln Asp Tyr Ser 305 310 315 320 Lys Arg Thr Ser Met Val Ala Ser Thr Met Ala His Glu Met Gly His 325 330 335 Asn Leu Gly Ile Asn His Asp Arg Ala Ser Cys Thr Ser Cys Gly Ser 340 345 350 Asn Lys Cys Ile Met Ser Thr Lys Arg Thr Lys Pro Ala Tyr Arg Phe 355 360 365 Ser Ser Cys Ser Val Arg Glu His Arg Arg Tyr Leu Leu Arg Asp Arg 370 375 380 Pro Gln Cys Ile Leu Asn Lys Pro Leu Ile Thr Asp Ile Val Ala Pro 385 390 395 400 Ala Ile Cys Gly Asn Tyr Phe Val Glu Val Gly Glu Glu Cys Asp Cys 405 410 415 Gly Ser Pro Arg Asp Cys Gln Ser Ala Cys Cys Asn Ala Ala Thr Cys 420 425 430 Lys Leu Lys His Gly Ala Gln Cys Asp Ser Gly Glu Cys Cys Arg Lys 435 440 445 Cys Lys Phe Lys Lys Ala Gly Ala Lys Cys Arg Ala Val Lys Asp Asp 450 455 460 Cys Asp Leu Pro Glu Arg Cys Thr Gly Arg Ser Ala Glu Cys Pro Thr 465 470 475 480 Asp Ile Phe Arg Arg Asn Gly Leu Pro Cys Gln Asn Asn Gln Gly Tyr 485 490 495 Cys Tyr Asn Gly Lys Cys Pro Thr Leu Thr Asn Gln Cys Ile Ala Phe 500 505 510 Met Gly Pro Asn Val Lys Val Ser Arg Asp Ser Cys Phe Thr Leu Asn 515 520 525 Gln Arg Gly Lys Gly Cys Gly Tyr Cys Arg Met Gln Asn Gly Ala Lys 530 535 540 Phe Pro Cys Ala Ala Lys Asp Ile Lys Cys Gly Lys Leu Phe Cys Lys 545 550 555 560 Lys Arg Asn Ser Lys Ile Cys Asn Cys Leu Ile Ser Pro Asp Asp Pro 565 570 575 Asn Tyr Gly Met Val Glu Pro Gly Thr Lys Cys Gly Asp Gly Val Val 580 585 590 Cys Ser Asn Arg Lys Cys Val Lys Leu Gln Arg Val Tyr 595 600 605 <210> 67 <211> 613 <212> PRT <213> Chinese cobra <400> 67 Met Ile Gln Ala Leu Leu Val Ile Ile Cys Leu Ala Val Phe Pro His 1 5 10 15 Gln Gly Ser Ser Ile Ile Leu Glu Ser Gly Asn Val Asn Asp Tyr Glu 20 25 30 Val Val Tyr Pro Gln Lys Val Pro Ala Leu Leu Lys Gly Gly Val Gln 35 40 45 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr Met Arg Tyr Glu Phe 50 55 60 Gln Val Asn Gly Glu Pro Val Val Leu His Leu Glu Arg Asn Lys Gly 65 70 75 80 Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Pro Asp Gly Arg 85 90 95 Glu Ile Thr Thr Ser Pro Pro Val Gln Asp His Cys Tyr Tyr His Gly 100 105 110 Tyr Ile Gln Asn Glu Ala Asp Ser Ser Ala Val Ile Ser Ala Cys Asp 115 120 125 Gly Leu Lys Gly His Phe Glu His Gln Gly Glu Thr Tyr Phe Ile Glu 130 135 140 Pro Leu Lys Ile Ser Asn Ser Glu Ala His Ala Ile Tyr Lys Asp Glu 145 150 155 160 Asn Val Glu Asn Glu Asp Glu Thr Pro Glu Ile Cys Gly Val Thr Glu 165 170 175 Thr Thr Trp Glu Ser Asp Glu Ser Ile Glu Lys Thr Ser Gln Leu Thr 180 185 190 Asn Thr Pro Glu Gln Asp Arg Tyr Leu Gln Ala Lys Lys Tyr Ile Glu 195 200 205 Phe Tyr Val Val Val Asp Asn Ile Met Tyr Arg His Tyr Lys Arg Asp 210 215 220 Gln Pro Val Ile Lys Arg Lys Val Tyr Glu Met Ile Asn Thr Met Asn 225 230 235 240 Met Ile Tyr Arg Arg Leu Asn Phe His Ile Ala Leu Ile Gly Leu Glu 245 250 255 Ile Trp Ser Asn Ile Asn Glu Ile Asn Val Gln Ser Asp Val Arg Ala 260 265 270 Thr Leu Asn Leu Phe Gly Glu Trp Arg Glu Lys Lys Leu Leu Pro Arg 275 280 285 Lys Arg Asn Asp Asn Ala Gln Leu Leu Thr Gly Ile Asp Phe Asn Gly 290 295 300 Thr Pro Val Gly Leu Ala Tyr Ile Gly Ser Ile Cys Asn Pro Lys Thr 305 310 315 320 Ser Ala Ala Val Val Gln Asp Tyr Ser Ser Arg Thr Arg Met Val Ala 325 330 335 Ile Thr Met Ala His Glu Met Gly His Asn Leu Gly Met Asn His Asp 340 345 350 Arg Gly Phe Cys Thr Cys Gly Phe Asn Lys Cys Val Met Ser Thr Arg 355 360 365 Arg Thr Lys Pro Ala Tyr Gln Phe Ser Ser Cys Ser Val Arg Glu His 370 375 380 Gln Arg Tyr Leu Leu Arg Asp Arg Pro Gln Cys Ile Leu Asn Lys Pro 385 390 395 400 Leu Ser Thr Asp Ile Val Ser Pro Pro Ile Cys Gly Asn Tyr Phe Val 405 410 415 Glu Val Gly Glu Glu Cys Asp Cys Gly Ser Pro Ala Asp Cys Gln Ser 420 425 430 Ala Cys Cys Asn Ala Thr Thr Cys Lys Leu Gln His Glu Ala Gln Cys 435 440 445 Asp Ser Glu Glu Cys Cys Glu Lys Cys Lys Phe Lys Gly Ala Arg Ala 450 455 460 Glu Cys Arg Ala Ala Lys Asp Asp Cys Asp Leu Pro Glu Leu Cys Thr 465 470 475 480 Gly Gln Ser Ala Glu Cys Pro Thr Asp Val Phe Gln Arg Asn Gly Leu 485 490 495 Pro Cys Gln Asn Asn Gln Gly Tyr Cys Tyr Asn Gly Lys Cys Pro Ile 500 505 510 Met Thr Asn Gln Cys Ile Ala Leu Arg Gly Pro Gly Val Lys Val Ser 515 520 525 Arg Asp Ser Cys Phe Thr Leu Asn Gln Arg Thr Arg Gly Cys Gly Leu 530 535 540 Cys Arg Met Glu Tyr Gly Arg Lys Ile Pro Cys Ala Ala Lys Asp Val 545 550 555 560 Lys Cys Gly Arg Leu Phe Cys Lys Arg Arg Asn Ser Met Ile Cys Asn 565 570 575 Cys Ser Ile Ser Pro Arg Asp Pro Asn Tyr Gly Met Val Glu Pro Gly 580 585 590 Thr Lys Cys Gly Asp Gly Met Val Cys Ser Asn Arg Gln Cys Val Asp 595 600 605 Val Lys Thr Ala Tyr 610 <210> 68 <211> 593 <212> PRT <213> Chinese cobra <400> 68 Met Ile Gln Ala Leu Leu Val Ile Ile Cys Leu Ala Val Phe Pro His 1 5 10 15 Gln Gly Ser Ser Ile Ile Leu Glu Ser Gly Asn Val Asn Asp Tyr Glu 20 25 30 Val Val Tyr Pro Gln Lys Val Pro Ala Leu Leu Lys Gly Gly Val Gln 35 40 45 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr Met Arg Tyr Glu Phe 50 55 60 Gln Val Asn Gly Glu Pro Val Val Leu His Leu Glu Arg Asn Lys Gly 65 70 75 80 Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Pro Asp Gly Arg 85 90 95 Glu Ile Thr Thr Ser Pro Pro Val Gln Asp His Cys Tyr Tyr His Gly 100 105 110 Tyr Ile Gln Asn Glu Ala Asp Ser Ser Ala Val Ile Ser Ala Cys Asp 115 120 125 Gly Leu Lys Gly His Phe Glu His Gln Gly Glu Thr Tyr Phe Ile Glu 130 135 140 Pro Leu Lys Ile Ser Asn Ser Glu Ala His Ala Ile Tyr Lys Asp Glu 145 150 155 160 Asn Val Glu Asn Glu Asp Glu Thr Pro Glu Ile Cys Gly Val Thr Glu 165 170 175 Thr Thr Trp Glu Ser Asp Glu Ser Ile Glu Lys Thr Ser Gln Leu Thr 180 185 190 Asn Thr Pro Glu Gln Asp Arg Tyr Leu Gln Asp Lys Lys Tyr Ile Glu 195 200 205 Phe Tyr Val Ile Val Asp Asn Arg Met Tyr Arg Tyr Tyr Asn Asn Asp 210 215 220 Lys Pro Ala Ile Lys Ile Arg Val Tyr Glu Met Ile Asn Ala Val Asn 225 230 235 240 Thr Lys Phe Arg Pro Leu Lys Ile His Ile Ala Leu Ile Gly Leu Glu 245 250 255 Ile Trp Ser Asn Lys Asp Lys Phe Glu Val Lys Pro Ala Ala Ser Val 260 265 270 Thr Leu Lys Ser Phe Gly Glu Trp Arg Glu Thr Val Leu Leu Pro Arg 275 280 285 Lys Arg Asn Asp Asn Ala Gln Leu Leu Thr Gly Ile Asp Phe Asn Gly 290 295 300 Asn Thr Val Gly Arg Ala Tyr Ile Gly Ser Leu Cys Lys Thr Asn Glu 305 310 315 320 Ser Val Ala Ile Val Gln Asp Tyr Asn Arg Arg Ile Ser Leu Val Ala 325 330 335 Ser Thr Met Thr His Glu Leu Gly His Asn Leu Gly Ile His His Asp 340 345 350 Lys Ala Ser Cys Ile Cys Ile Pro Gly Pro Cys Ile Met Leu Lys Lys 355 360 365 Arg Thr Ala Pro Ala Phe Gln Phe Ser Ser Cys Ser Ile Arg Glu Tyr 370 375 380 Arg Glu Tyr Leu Leu Arg Asp Arg Pro Gln Cys Ile Leu Asn Lys Pro 385 390 395 400 Leu Ser Thr Asp Ile Val Ser Pro Pro Ile Cys Gly Asn Tyr Phe Val 405 410 415 Glu Val Gly Glu Glu Cys Asp Cys Gly Ser Pro Gln Ala Cys Gln Ser 420 425 430 Ala Cys Cys Asn Ala Ala Thr Cys Gln Phe Lys Gly Ala Glu Thr Glu 435 440 445 Cys Arg Val Ala Lys Asp Asp Cys Asp Leu Pro Glu Leu Cys Thr Gly 450 455 460 Gln Ser Ala Glu Cys Pro Thr Asp Ser Leu Gln Arg Asn Gly His Pro 465 470 475 480 Cys Gln Asn Asn Gln Gly Tyr Cys Tyr Asn Arg Thr Cys Pro Thr Leu 485 490 495 Thr Asn Gln Cys Ile Thr Leu Leu Gly Pro His Phe Thr Val Ser Pro 500 505 510 Lys Gly Cys Phe Asp Leu Asn Met Arg Gly Asp Asp Gly Ser Phe Cys 515 520 525 Gly Met Glu Asp Gly Thr Lys Ile Pro Cys Ala Ala Lys Asp Val Lys 530 535 540 Cys Gly Arg Leu Tyr Cys Thr Glu Lys Asn Thr Met Ser Cys Leu Ile 545 550 555 560 Pro Pro Asn Pro Asp Gly Ile Met Ala Glu Pro Gly Thr Lys Cys Gly 565 570 575 Asp Gly Met Val Cys Ser Lys Gly Gln Cys Val Asp Val Gln Thr Ala 580 585 590 Tyr <210> 69 <211> 593 <212> PRT <213> Chinese cobra <400> 69 Met Ile Gln Ala Leu Leu Val Ile Ile Cys Leu Ala Val Phe Pro His 1 5 10 15 Gln Gly Ser Ser Ile Ile Leu Glu Ser Gly Asn Val Asn Asp Tyr Glu 20 25 30 Val Val Tyr Pro Gln Lys Val Pro Ala Leu Leu Lys Gly Gly Val Gln 35 40 45 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr Met Arg Tyr Glu Phe 50 55 60 Gln Val Asn Gly Glu Pro Val Val Leu His Leu Glu Arg Asn Lys Gly 65 70 75 80 Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Pro Asp Gly Arg 85 90 95 Glu Ile Thr Thr Ser Pro Pro Val Gln Asp His Cys Tyr Tyr His Gly 100 105 110 Tyr Ile Gln Asn Glu Ala Asp Ser Ser Ala Val Ile Ser Ala Cys Asp 115 120 125 Gly Leu Lys Gly His Phe Glu His Gln Gly Glu Thr Tyr Phe Ile Glu 130 135 140 Pro Leu Lys Ile Ser Asn Ser Glu Ala His Ala Ile Tyr Lys Asp Glu 145 150 155 160 Asn Val Glu Asn Glu Asp Glu Thr Pro Glu Ile Cys Gly Val Thr Glu 165 170 175 Thr Thr Trp Glu Ser Asp Glu Ser Ile Glu Lys Thr Ser Gln Phe Thr 180 185 190 Asn Thr Pro Glu Gln Asp Arg Tyr Leu Gln Asp Lys Lys Tyr Ile Glu 195 200 205 Phe Tyr Val Ile Val Asp Asn Arg Met Tyr Arg Tyr Tyr Asn Asn Asp 210 215 220 Lys Pro Ala Ile Lys Ile Arg Val Tyr Glu Met Ile Asn Ala Val Asn 225 230 235 240 Thr Lys Phe Arg Pro Leu Lys Ile His Ile Ala Leu Ile Gly Leu Glu 245 250 255 Ile Trp Ser Asn Lys Asp Lys Phe Glu Val Lys Pro Ala Ala Ser Val 260 265 270 Thr Leu Lys Ser Phe Gly Glu Trp Arg Glu Thr Val Leu Leu Pro Arg 275 280 285 Lys Arg Asn Asp Asn Ala Gln Leu Leu Thr Gly Ile Asp Phe Asn Gly 290 295 300 Asn Thr Val Gly Arg Ala Tyr Ile Gly Ser Leu Cys Lys Thr Asn Glu 305 310 315 320 Ser Val Ala Ile Val Gln Asp Tyr Asn Arg Arg Ile Ser Leu Val Ala 325 330 335 Ser Thr Ile Thr His Glu Leu Gly His Asn Leu Gly Ile His His Asp 340 345 350 Lys Ala Ser Cys Ile Cys Ile Pro Gly Pro Cys Ile Met Leu Lys Lys 355 360 365 Arg Thr Ala Pro Ala Phe Gln Phe Ser Ser Cys Ser Ile Arg Glu Tyr 370 375 380 Arg Glu Tyr Leu Leu Arg Asp Arg Pro Gln Cys Ile Leu Asn Lys Pro 385 390 395 400 Leu Ser Thr Asp Ile Val Ser Pro Pro Ile Cys Gly Asn Tyr Phe Val 405 410 415 Glu Val Gly Glu Glu Cys Asp Cys Gly Ser Pro Gln Ala Cys Gln Ser 420 425 430 Ala Cys Cys Asn Ala Ala Thr Cys Gln Phe Lys Gly Ala Glu Thr Glu 435 440 445 Cys Arg Val Ala Lys Asp Asp Cys Asp Leu Pro Glu Leu Cys Thr Gly 450 455 460 Gln Ser Ala Glu Cys Pro Thr Asp Ser Leu Gln Arg Asn Gly His Pro 465 470 475 480 Cys Gln Asn Asn Gln Ser Tyr Cys Tyr Asn Gly Thr Cys Pro Thr Leu 485 490 495 Thr Asn Gln Cys Ile Thr Leu Leu Gly Pro His Phe Thr Val Ser Pro 500 505 510 Lys Gly Cys Phe Asp Leu Asn Met Arg Gly Asp Asp Gly Ser Phe Cys 515 520 525 Arg Met Glu Asp Gly Thr Lys Ile Pro Cys Ala Ala Lys Asp Val Lys 530 535 540 Cys Gly Arg Leu Tyr Cys Thr Glu Lys Asn Thr Met Ser Cys Leu Ile 545 550 555 560 Pro Pro Asn Pro Asp Gly Ile Met Ala Glu Pro Gly Thr Lys Cys Gly 565 570 575 Asp Gly Met Val Cys Ser Lys Gly Gln Cys Val Asp Val Gln Thr Ala 580 585 590 Tyr <210> 70 <211> 621 <212> PRT <213> Chinese cobra <400> 70 Met Ile Gln Pro Leu Leu Val Ala Ile Cys Leu Val Val Phe Pro Tyr 1 5 10 15 Gln Gly Ser Ser Thr Ile Leu Glu Ser Gly Lys Val Arg Asp Tyr Glu 20 25 30 Val Val Tyr Pro Gln Lys Ile Pro Ser Leu Pro Lys Gly Arg Leu Gln 35 40 45 Arg Arg Glu Glu Lys Thr Lys Tyr Glu Asn Thr Met Lys Tyr Glu Phe 50 55 60 Lys Val Asn Gly Glu Pro Val Val Leu Asn Leu Glu Lys Asn Lys Arg 65 70 75 80 Leu Phe Ser Lys Asp Tyr Thr Glu Thr His Tyr Ser Pro Asp Gly Arg 85 90 95 Glu Ile Thr Thr Ser Pro Pro Val Gln Asp His Cys Tyr Tyr His Gly 100 105 110 His Ile Gln Asn Asp Ala Asp Ser Thr Ala Val Ile Arg Ala Cys Asp 115 120 125 Gly Leu Asn Gly Tyr Phe Lys Ser Asn Gly Glu Met Tyr Ile Ile Glu 130 135 140 Pro Leu Lys Leu Ser Asp Ser Glu Ala His Ala Val Phe Lys Tyr Glu 145 150 155 160 Ser Leu Glu Lys Glu Asp Glu Thr Pro Lys Thr Cys Gly Ala Ile His 165 170 175 Asn Ser Gly Glu Ser Asp Glu Thr Ile Lys Lys Ile Ser Asn Thr Phe 180 185 190 Val Thr Pro Glu Lys Gly Glu Glu Tyr Leu Glu Ala Glu Lys His Ile 195 200 205 Glu Leu Tyr Met Val Ala Asp Asn Leu Val Tyr Arg Lys Tyr Ser Ser 210 215 220 Asn Ile Thr Val Val Arg Met Arg Ile Phe Glu Ile Leu Asn Tyr Val 225 230 235 240 Asn Leu Tyr Tyr Lys Ile Leu Asn Ile His Val Val Leu Ile Gly Leu 245 250 255 Glu Val Trp Ser Asp Glu Asp Lys Ile Leu Ile Asn Gly Ser Ser Glu 260 265 270 Leu Thr Val Arg Ser Phe Ala Ala Trp Arg His Ser Asp Leu Leu Lys 275 280 285 His Lys Arg Asn Asp Asn Ala Gln Leu Leu Thr Gly Ile His Phe Asp 290 295 300 Lys Arg Val Leu Gly Ile Ala Phe Ile Gly Gly Met Cys Asn Asn Phe 305 310 315 320 Thr Ser Val Gly Ala Ile Gln Asp Asn Ser Ile His Ala Val Leu Ile 325 330 335 Ala Ala Thr Met Thr His Glu Leu Gly His Asn Leu Gly Met Asn His 340 345 350 Asp Thr Asp Ser Cys Thr Cys Asn Thr Gly Pro Cys Ile Met Lys Ala 355 360 365 Ala Leu Asn Phe Lys Pro Pro Tyr Glu Phe Ser Ser Cys Ser Tyr Trp 370 375 380 Asp Phe Gln Asn Tyr Ile Met Thr Lys Ser Ala Gln Cys Ile Leu Asn 385 390 395 400 Asp Pro Leu Thr Thr Asp Ile Val Pro Thr Ala Ile Cys Gly Asn Gly 405 410 415 Phe Val Glu Glu Gly Glu Glu Cys Asp Cys Gly Pro Pro Glu Ile Cys 420 425 430 Lys Asn Glu Cys Cys Glu Ala Ala Thr Cys Lys Leu Lys Pro Glu Ala 435 440 445 Gln Cys Ala Ser Gly Ala Cys Cys Glu Glu Cys Gln Phe Arg Arg Ala 450 455 460 Gly Glu Leu Cys Arg Ala Ala Lys Asp Asp Cys Asp Leu Asp Glu Leu 465 470 475 480 Cys Thr Gly Gln Ser Ala Glu Cys Pro Met Asn His Phe His Met Asn 485 490 495 Gly His Pro Cys Gln Asn Asn Gln Gly Tyr Cys Phe Arg Gly Thr Cys 500 505 510 Pro Thr Leu Thr Lys Gln Cys Ile Ala Leu Trp Gly Pro Asp Ala Glu 515 520 525 Val Ala Pro Asp Gly Cys Phe Met Asn Asn Gln Lys Gly Asn Tyr Tyr 530 535 540 Gly Tyr Cys Lys Lys Lys Asn Gly Thr Asn Ile Pro Cys Glu Pro Glu 545 550 555 560 Asn Val Lys Cys Gly Arg Leu Tyr Cys Ile Asp Asp Ser Thr Glu Glu 565 570 575 Asn Ser Cys Lys Phe His Phe Ser Asn Glu Asn Ala Asn Ser Gly Met 580 585 590 Val Gln Pro Gly Thr Lys Cys Gly Glu Gly Met Val Cys Gly Phe Gly 595 600 605 Glu Cys Ile Gly Leu Glu Thr Ala Leu Gly Ile Asn Gln 610 615 620 <210> 71 <211> 607 <212> PRT <213> Chinese cobra <400> 71 Met Ile Gln Ala Leu Leu Val Ile Ile Cys Leu Ala Val Phe Pro His 1 5 10 15 Gln Gly Ser Ser Ile Ile Leu Glu Ser Gly Asn Val Asn Asp Tyr Glu 20 25 30 Val Val Tyr Pro Gln Lys Val Pro Ala Leu Leu Lys Gly Gly Val Gln 35 40 45 Asn Pro Gln Pro Glu Thr Lys Tyr Glu Asp Thr Met Arg Tyr Glu Phe 50 55 60 Gln Val Asn Gly Glu Pro Val Val Leu His Leu Glu Arg Asn Lys Gly 65 70 75 80 Leu Phe Ser Glu Asp Tyr Thr Glu Thr His Tyr Ala Pro Asp Gly Arg 85 90 95 Glu Ile Thr Thr Ser Pro Pro Val Gln Asp His Cys Tyr Tyr His Gly 100 105 110 Tyr Ile Gln Asn Glu Ala Asp Ser Ser Ala Val Ile Ser Ala Cys Asn 115 120 125 Gly Leu Lys Gly His Phe Lys His Gln Gly Glu Thr Tyr Phe Ile Glu 130 135 140 Pro Leu Glu Leu Ser Glu Ser Glu Ala His Ala Ile Tyr Lys Asp Glu 145 150 155 160 Asn Val Glu Lys Glu Asp Glu Thr Pro Lys Ile Cys Ala Val Thr Gln 165 170 175 Thr Thr Trp Glu Ser Asp Glu Ser Ile Glu Lys Thr Ser Gln Leu Thr 180 185 190 Asn Thr Pro Glu Gln Asp Arg Tyr Leu Gln Val Lys Lys Tyr Ile Glu 195 200 205 Phe Tyr Leu Val Val Asp Asn Lys Met Tyr Lys Asn His Thr Ser Asn 210 215 220 Gln Glu Leu Arg Thr Arg Val Tyr Glu Met Val Asn Tyr Leu Asn Thr 225 230 235 240 Lys Tyr Arg Arg Leu Asn Phe His Ile Ala Leu Ile Gly Leu Glu Ile 245 250 255 Trp Ser Asn Gln Asp Lys Val Asp Met Asp Pro Gly Ala Asn Val Thr 260 265 270 Leu Lys Ser Phe Ala Glu Trp Arg Ala Lys Leu Pro Pro His Lys Arg 275 280 285 Asn Asp Asn Ala Gln Leu Leu Thr Gly Ile Asp Phe Asn Gly Thr Thr 290 295 300 Val Gly Leu Ala Tyr Thr Gly Thr Leu Cys Thr Trp Gly Ser Val Ala 305 310 315 320 Val Val Gln Asp Tyr Ser Arg Arg Thr Ile Leu Met Ala Ser Thr Met 325 330 335 Ala His Glu Leu Gly His Asn Met Gly Ile His His Asp Lys Ala Asn 340 345 350 Cys Arg Cys Ser His Ser Pro Cys Ile Met Ser Asp Thr Ile Ser Asp 355 360 365 Glu Pro Phe Tyr Glu Phe Ser Ser Cys Ser Val Arg Glu His Gln Glu 370 375 380 Tyr Leu Leu Arg Glu Arg Pro Gln Cys Ile Leu Asn Lys Pro Ser Arg 385 390 395 400 Lys Ala Ile Val Ser Arg Pro Val Cys Gly Asn Asn Phe Val Glu Val 405 410 415 Gly Glu Gln Cys Asp Cys Gly Ser Leu Gln Asp Cys Gln Ser Thr Cys 420 425 430 Cys Asn Ala Thr Thr Cys Lys Leu Gln Pro His Ala Gln Cys Asp Ser 435 440 445 Glu Glu Cys Cys Glu Lys Cys Lys Phe Lys Gly Ala Glu Thr Glu Cys 450 455 460 Arg Ala Ala Lys Asp Asp Cys Asp Leu Pro Glu Phe Cys Thr Gly Gln 465 470 475 480 Ser Ala Glu Cys Pro Thr Asp Ser Leu Gln Arg Asn Gly His Pro Cys 485 490 495 Gln Asn Asn Gln Gly Tyr Cys Tyr Asn Gly Lys Cys Pro Thr Met Glu 500 505 510 Asn Gln Cys Ile Thr Leu Leu Gly Pro Asn Tyr Thr Val Gly Pro Ala 515 520 525 Gly Cys Phe Lys Asn Asn Arg Lys Gly Asp Asp Val Ser His Cys Arg 530 535 540 Lys Glu Asn Gly Ala Lys Ile Pro Cys Ala Ala Lys Asp Glu Lys Cys 545 550 555 560 Gly Thr Leu Tyr Cys Thr Glu Ile Lys Lys Thr Gly Cys Ile Val Pro 565 570 575 Val Ser Pro Arg Asp Pro Asp Ser Arg Met Val Glu Pro Gly Thr Lys 580 585 590 Cys Glu Asp Lys Lys Val Cys Ser Lys Ser Gln Cys Val Lys Val 595 600 605 <210> 72 <211> 611 <212> PRT <213> Chinese cobra <400> 72 Met Ile Gln Val Leu Leu Val Thr Ile Cys Leu Val Val Phe Pro Tyr 1 5 10 15 Gln Gly Ser Ser Ile Ile Leu Glu Ser Gly Lys Val Asn Asp Tyr Glu 20 25 30 Val Val Tyr Pro Gln Lys Ile Pro Val Leu Pro Lys Ser Lys Ile Gln 35 40 45 Arg Arg Glu Gln Lys Met Tyr Glu Asp Thr Met Lys Tyr Glu Phe Lys 50 55 60 Val Asn Gly Glu Pro Val Val Leu His Leu Glu Arg Asn Lys Glu Leu 65 70 75 80 Phe Ser Lys Asp Tyr Thr Glu Thr His Tyr Ser Pro Asp Gly Arg Glu 85 90 95 Ile Thr Thr Ser Pro Pro Val Glu Asp His Cys Tyr Tyr His Gly Tyr 100 105 110 Ile Gln Ser Asp Ile Asp Ser Thr Ala Ile Leu Asn Ala Cys Asn Gly 115 120 125 Leu Lys Gly Tyr Phe Arg His His Gly Glu Ala Tyr His Ile Glu Pro 130 135 140 Leu Lys Phe Ser Asp Ser Glu Ala His Ala Val Tyr Lys Tyr Glu Asn 145 150 155 160 Ile Glu Lys Glu Asp Glu Thr Pro Lys Ile Cys Gly Val Lys His Ser 165 170 175 Thr Trp Glu Ser Asp Glu Pro Ile Glu Lys Ile Ser Gln Lys Lys Asp 180 185 190 Phe Leu Glu Glu Lys Lys Tyr Leu Glu Leu Tyr Ile Val Ala Asp Tyr 195 200 205 Val Met Phe Arg Lys Tyr Gly Arg Asn Val Thr Thr Ile Arg Met Arg 210 215 220 Val Phe Asp Met Val Asn Tyr Ile Thr Val Val Tyr Lys Ala Leu Asn 225 230 235 240 Ile His Val Ala Leu Ile Gly Phe Glu Ile Trp Ser Leu Lys Asp Lys 245 250 255 Phe Val Ile Asn Ala Ser Thr Lys Asn Asn Leu Leu His Phe Ser Ile 260 265 270 Trp Arg Ser Thr Val Leu Arg Lys Arg Asn Asp Asn Ala Gln Leu Leu 275 280 285 Thr Gly Val Asp Leu Asn Gly Tyr Thr Leu Gly Ser Ala Tyr Leu Lys 290 295 300 Ala Met Cys Asp Val Leu Gln Ser Val Gly Ile Val Gln Asp Tyr Ser 305 310 315 320 Lys Ser Pro Tyr Leu Val Gly Ala Ala Met Ala His Glu Ile Gly His 325 330 335 Asn Leu Gly Met Glu His Asp Thr Lys Thr Cys Ser Cys Met Arg Gly 340 345 350 Asn Cys Ile Met Ser Pro Glu Glu Glu Gly Ser Asp Phe Pro Met Glu 355 360 365 Phe Ser Ser Cys Ser Leu Tyr Asp Phe Gln Asn Tyr Met Leu Thr Asp 370 375 380 Thr Pro Gln Cys Leu Ile Asn Lys Pro Ser Asn Thr Ser Ile Ile Lys 385 390 395 400 Asn Ala Val Cys Gly Asn Tyr Val Glu Glu Glu Gly Glu Glu Cys Asp 405 410 415 Cys Gly Ser Pro Glu Gln Cys Glu Asn Asn Cys Cys Glu Ala Ala Thr 420 425 430 Cys Lys Leu Lys Pro Gly Ala Lys Cys Ala Lys Gly Ala Cys Cys Lys 435 440 445 Lys Cys Gln Phe Lys Lys Ala Gly Ala Glu Cys Arg Ala Ala Arg Asn 450 455 460 Glu Cys Asp Leu Pro Glu Phe Cys Ile Gly Gln Ser Ala Glu Cys Pro 465 470 475 480 Met Asp Arg Phe His Lys Asn Gly His Ser Cys Gln Asn Asp Gln Gly 485 490 495 Tyr Cys Phe Arg Gly Tyr Cys Pro Thr Leu Ala Lys Gln Cys Ile Thr 500 505 510 Leu Trp Gly Ser Asp Ala Lys Val Ala Pro Asp Glu Cys Phe Gln Asn 515 520 525 Asn Thr Asn Gly Asn Glu Tyr Asp Tyr Cys Lys Lys Thr Asn Asn Val 530 535 540 Ile Ile Pro Cys Lys Pro Thr Asp Val Lys Cys Gly Arg Leu Tyr Cys 545 550 555 560 Thr Gly Gly Thr Glu Asn Pro Ser Glu Gly Glu Lys Ile Ser Ser Asp 565 570 575 Pro Cys Lys Ala Ser Tyr Ser Glu Ile Glu Asp Ile Gly Met Val Asp 580 585 590 His Arg Thr Lys Cys Gly Glu Lys Met Val Cys Ser Asp Gly Lys Cys 595 600 605 Ile Pro Leu 610 <210> 73 <211> 86 <212> PRT <213> Banded krait <400> 73 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Thr Cys Leu Ile Cys Pro Glu Arg Tyr Cys 20 25 30 Gln Lys Val His Thr Cys Arg Gly Glu Glu Lys Leu Cys Val Lys Arg 35 40 45 Phe Tyr Asp Glu Lys Ala Leu Gly Trp Arg Ala Lys Arg Gly Cys Ala 50 55 60 Ala Thr Cys Pro Glu Ala Lys Pro Lys Glu Thr Val Glu Cys Cys Ser 65 70 75 80 Thr Asp Lys Cys Asn Lys 85 <210> 74 <211> 86 <212> PRT <213> Banded krait <400> 74 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Thr Cys Leu Ile Cys Pro Glu Lys Tyr Cys 20 25 30 Gln Lys Val His Thr Cys Arg Asp Gly Glu Asn Leu Cys Val Lys Arg 35 40 45 Phe Tyr Glu Gly Lys Arg Phe Gly Lys Lys Tyr Pro Arg Gly Cys Ala 50 55 60 Ala Thr Cys Pro Glu Ala Lys Pro His Glu Ile Val Glu Cys Cys Ser 65 70 75 80 Thr Asp Lys Cys Asn Lys 85 <210> 75 <211> 78 <212> PRT <213> Banded krait <400> 75 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys His Thr Thr Gln Phe Arg Asn Ile 20 25 30 Glu Thr Cys Gln Lys Trp Glu Thr Val Cys Phe Gln Arg Ala Val Lys 35 40 45 Pro His Pro Ser Ser Met Ile Val Leu Arg Gly Cys Thr Ser Ser Cys 50 55 60 Gly Lys Gly Glu Thr Cys Cys Ala Thr Asp Leu Cys Asn Arg 65 70 75 <210> 76 <211> 79 <212> PRT <213> Banded krait <400> 76 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys Tyr Ser Ser Ser Met Asn Lys Asp 20 25 30 Ser Lys Thr Cys Gln Lys Trp Glu Thr Val Cys Phe Gln Glu Ala Phe 35 40 45 Lys Pro His Ser Ser Gly Met Ile Ile Leu Arg Gly Cys Ala Ser Ser 50 55 60 Cys Pro Lys Gly Tyr Thr Cys Cys Ala Thr Asp Leu Cys Asn Trp 65 70 75 <210> 77 <211> 86 <212> PRT <213> Banded krait <400> 77 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Glu Leu Gly Tyr Thr Arg Lys Cys Leu Thr Lys Tyr Ser Gln Asp Asn 20 25 30 Glu Ser Ser Lys Thr Cys Pro Ser Gly Gln Lys Leu Cys Phe Lys Lys 35 40 45 Trp Glu Thr Gly Lys Leu Leu Gly Thr Lys Val Lys Arg Gly Cys Val 50 55 60 Ala Thr Cys Pro Gln Pro Lys Lys Glu Trp Ile Ile Gln Cys Cys Ala 65 70 75 80 Lys Asp Lys Cys Asn Lys 85 <210> 78 <211> 63 <212> PRT <213> Banded krait <400> 78 Leu Lys Cys His Lys Ala Gln Phe Pro Asn Ile Glu Thr Gln Cys Lys 1 5 10 15 Trp Gln Thr Leu Cys Phe Gln Arg Asp Val Lys Pro His Pro Ser Ser 20 25 30 Met Ile Val Leu Arg Gly Cys Thr Ser Ser Cys Gly Lys Gly Ala Met 35 40 45 Cys Cys Ala Thr Asp Leu Cys Asn Gly Pro Ser Thr Pro Ser Thr 50 55 60 <210> 79 <211> 64 <212> PRT <213> Banded krait <400> 79 Arg Ile Cys Leu Asn Gln Gln Gln Ser Thr Pro Glu Asp Gln Pro Thr 1 5 10 15 Asn Gly Gln Cys Tyr Ile Lys Thr Asp Cys Gln Asn Lys Thr Trp Asn 20 25 30 Thr His Arg Gly Ser Arg Thr Asp Arg Gly Cys Gly Cys Pro Lys Val 35 40 45 Lys Pro Gly Ile Asn Leu Arg Cys Cys Lys Thr Asp Lys Cys Asn Glu 50 55 60 <210> 80 <211> 83 <212> PRT <213> Banded krait <400> 80 Met Lys Thr Leu Leu Leu Thr Leu Val Val Leu Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly His Thr Arg Ile Cys Leu Asn Gln Gln Ser Ser Glu Pro 20 25 30 Gln Thr Thr Glu Thr Cys Pro Asn Gly Glu Asp Thr Cys Tyr Asn Lys 35 40 45 Thr Trp Asn Thr His Arg Gly Ser Arg Thr Asp Arg Gly Cys Gly Cys 50 55 60 Pro Lys Val Lys Pro Gly Ile Asn Leu Arg Cys Cys Lys Thr Asp Lys 65 70 75 80 Cys Asn Gln <210> 81 <211> 83 <212> PRT <213> Chinese cobra <400> 81 Met Lys Thr Leu Leu Leu Thr Leu Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Glu Cys His Asn Gln Gln Ser Ser Gln Thr 20 25 30 Pro Thr Thr Thr Gly Cys Ser Gly Gly Glu Thr Asn Cys Tyr Lys Lys 35 40 45 Arg Trp Arg Asp His Arg Gly Tyr Arg Thr Glu Arg Gly Cys Gly Cys 50 55 60 Pro Ser Val Lys Asn Gly Ile Glu Ile Asn Cys Cys Thr Thr Asp Arg 65 70 75 80 Cys Asn Asn <210> 82 <211> 81 <212> PRT <213> Chinese cobra <400> 82 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ser Asn Leu Thr Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Ala Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 83 <211> 82 <212> PRT <213> Chinese cobra <400> 83 Met Lys Thr Leu Leu Leu Thr Leu Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Glu Cys His Asn Gln Gln Ser Ser Gln Thr 20 25 30 Pro Thr Thr Lys Thr Cys Ser Gly Glu Thr Asn Cys Tyr Lys Lys Trp 35 40 45 Trp Ser Asp His Arg Gly Thr Ile Ile Glu Arg Gly Cys Gly Cys Pro 50 55 60 Lys Val Lys Pro Gly Val Asn Leu Asn Cys Cys Thr Thr Asp Arg Cys 65 70 75 80 Asn Asn <210> 84 <211> 81 <212> PRT <213> Chinese cobra <400> 84 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ser Asn Leu Thr Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Ala Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 85 <211> 81 <212> PRT <213> Chinese cobra <400> 85 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Thr Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Ser Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 86 <211> 81 <212> PRT <213> Chinese cobra <400> 86 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Gln Leu Ile Pro Pro Phe Tyr 20 25 30 Lys Thr Cys Ala Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Ala Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Ser Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 87 <211> 81 <212> PRT <213> Chinese cobra <400> 87 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Ile Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Met 35 40 45 Ser Asp Leu Thr Ile Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 88 <211> 83 <212> PRT <213> Chinese cobra <400> 88 Met Lys Thr Leu Leu Leu Thr Met Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys His Asn Thr Gln Leu Pro Phe Ile 20 25 30 Tyr Lys Thr Cys Pro Glu Gly Lys Asn Leu Cys Phe Lys Ala Thr Leu 35 40 45 Lys Lys Phe Pro Leu Lys Phe Pro Val Lys Arg Gly Cys Ala Asp Asn 50 55 60 Cys Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Thr Asp 65 70 75 80 Lys Cys Asn <210> 89 <211> 60 <212> PRT <213> Chinese cobra <400> 89 Leu Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr Lys Thr Cys Pro Ala 1 5 10 15 Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val Ser Asn Lys Met Val 20 25 30 Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro Lys Ser Ser Leu Leu 35 40 45 Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys Asn 50 55 60 <210> 90 <211> 81 <212> PRT <213> Chinese cobra <400> 90 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Gln Leu Ile Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Met 35 40 45 Ser Asp Leu Thr Ile Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 91 <211> 81 <212> PRT <213> Chinese cobra <400> 91 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Ile Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Thr Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Ser Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 92 <211> 81 <212> PRT <213> Chinese cobra <400> 92 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Thr Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 93 <211> 81 <212> PRT <213> Chinese cobra <400> 93 Met Lys Thr Leu Leu Leu Thr Leu Ala Ala Ala Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Ile Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Met Asn Leu Cys Tyr Lys Met Phe Met Met 35 40 45 Ser Asp Leu Thr Ile Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 94 <211> 81 <212> PRT <213> Chinese cobra <400> 94 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Gln Leu Ile Pro Pro Phe Tyr 20 25 30 Lys Ala Cys Ala Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Ala Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Ser Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Looks <210> 95 <211> 81 <212> PRT <213> Chinese cobra <400> 95 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Ile Pro Ile Ala Ser 20 25 30 Lys Thr Cys Thr Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Met 35 40 45 Ser Asp Leu Thr Ile Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 96 <211> 86 <212> PRT <213> Chinese cobra <400> 96 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Thr Cys Leu Asn Cys Pro Glu Met Phe Cys 20 25 30 Gly Lys Phe Gln Ile Cys Arg Asn Gly Glu Lys Ile Cys Phe Lys Lys 35 40 45 Leu His Gln Arg Arg Pro Phe Ser Leu Arg Tyr Ile Arg Gly Cys Ala 50 55 60 Ala Thr Cys Pro Glu Thr Lys Pro Arg Asp Met Val Glu Cys Cys Ser 65 70 75 80 Thr Asp Arg Cys Asn Arg 85 <210> 97 <211> 60 <212> PRT <213> Chinese cobra <400> 97 Leu Lys Cys Lys Lys Leu Val Pro Leu Phe Ser Lys Thr Cys Pro Pro 1 5 10 15 Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val Ala Ala Pro Lys Val 20 25 30 Pro Val Lys Arg Gly Cys Ile Asn Val Cys Pro Lys Ser Ser Leu Leu 35 40 45 Val Lys Tyr Val Cys Cys Asn Thr Asp Lys Cys Asn 50 55 60 <210> 98 <211> 60 <212> PRT <213> Chinese cobra <400> 98 Leu Lys Cys Lys Lys Leu Val Pro Leu Phe Ser Lys Thr Cys Pro Pro 1 5 10 15 Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val Ala Thr Pro Lys Val 20 25 30 Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro Lys Ser Ser Leu Leu 35 40 45 Val Lys Tyr Val Cys Cys Asn Thr Asp Lys Cys Asn 50 55 60 <210> 99 <211> 81 <212> PRT <213> Chinese cobra <400> 99 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Thr Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Ala Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 100 <211> 81 <212> PRT <213> Chinese cobra <400> 100 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Ile Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Thr Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 101 <211> 60 <212> PRT <213> Chinese cobra <400> 101 Leu Lys Cys Asn Lys Leu Lys Pro Leu Ala Tyr Lys Thr Cys Pro Ala 1 5 10 15 Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Met Ser Asn Lys Thr Val 20 25 30 Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro Lys Asn Ser Leu Leu 35 40 45 Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys Asn 50 55 60 <210> 102 <211> 81 <212> PRT <213> Chinese cobra <400> 102 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ser Asn Leu Thr Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Ser Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 103 <211> 81 <212> PRT <213> Chinese cobra <400> 103 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Val Pro Leu Phe Tyr 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ser Asn Lys Met Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Ala Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 104 <211> 82 <212> PRT <213> Chinese cobra <400> 104 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Val Thr Ile Val Cys 1 5 10 15 Leu Asp Leu Gly Tyr Thr Leu Lys Cys Asn Gln His Ile Pro Pro Phe 20 25 30 Tyr Lys Thr Cys Ala Ala Gly Lys Asn Leu Cys Tyr Lys Ile Phe Met 35 40 45 Val Ala Ala Pro Lys Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys 50 55 60 Pro Lys Ser Ser Asp Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg 65 70 75 80 Cys Asn <210> 105 <211> 81 <212> PRT <213> Chinese cobra <400> 105 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Ile Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Met 35 40 45 Ser Asp Leu Thr Ile Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser His Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 106 <211> 81 <212> PRT <213> Chinese cobra <400> 106 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Pro Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Met 35 40 45 Ser Asp Leu Thr Ile Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Asn Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn <210> 107 <211> 81 <212> PRT <213> Chinese cobra <400> 107 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Lys Leu Val Pro Ile Ala Ser 20 25 30 Lys Thr Cys Pro Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Met 35 40 45 Ser Asp Leu Thr Val Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Ser Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Ile Cys 65 70 75 80 Asn <210> 108 <211> 60 <212> PRT <213> Chinese cobra <400> 108 Leu Lys Cys Lys Lys Leu Val Pro Leu Phe Ser Lys Thr Cys Pro Pro 1 5 10 15 Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val Ala Thr Pro Lys Val 20 25 30 Pro Val Lys Arg Glu Cys Ile Asp Val Cys Pro Lys Ser Ser Leu Leu 35 40 45 Val Lys Tyr Val Cys Cys Asn Thr Asp Lys Cys Asn 50 55 60 <210> 109 <211> 83 <212> PRT <213> Chinese cobra <400> 109 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys His Asn Thr Gln Leu Pro Phe Ile 20 25 30 Tyr Lys Thr Cys Pro Glu Gly Lys Asn Leu Cys Phe Lys Ala Thr Leu 35 40 45 Lys Lys Phe Pro Leu Lys Phe Pro Val Lys Arg Gly Cys Ala Asp Asn 50 55 60 Cys Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Thr Asp 65 70 75 80 Court of Assn <210> 110 <211> 82 <212> PRT <213> Chinese cobra <400> 110 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys Asn Gln Leu Ile Pro Pro Phe Tyr 20 25 30 Lys Thr Cys Ala Ala Gly Lys Asn Leu Cys Tyr Lys Met Phe Met Val 35 40 45 Ala Ala Gln Arg Phe Pro Val Lys Arg Gly Cys Ile Asp Val Cys Pro 50 55 60 Lys Ser Ser Leu Leu Val Lys Tyr Val Cys Cys Asn Thr Asp Arg Cys 65 70 75 80 Asn Asn <210> 111 <211> 83 <212> PRT <213> Chinese cobra <400> 111 Met Lys Thr Leu Leu Leu Thr Met Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys His Asn Thr Gln Leu Pro Phe Ile 20 25 30 Tyr Lys Thr Cys Pro Glu Gly Lys Asn Leu Cys Phe Lys Ala Thr Leu 35 40 45 Lys Lys Phe Pro Leu Lys Phe Pro Val Lys Arg Gly Cys Ala Asp Asn 50 55 60 Cys Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Ser Asp 65 70 75 80 Lys Cys Asn <210> 112 <211> 86 <212> PRT <213> Chinese cobra <400> 112 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Ala Leu Gly Tyr Thr Leu Thr Cys Leu Ile Cys Pro Glu Lys Tyr Cys 20 25 30 Asn Lys Val His Thr Cys Leu Asn Gly Glu Lys Ile Cys Phe Lys Lys 35 40 45 Tyr Asp Gln Arg Lys Leu Leu Gly Lys Arg Tyr Ile Arg Gly Cys Ala 50 55 60 Asp Thr Cys Pro Val Arg Lys Pro Arg Glu Ile Val Glu Cys Cys Ser 65 70 75 80 Thr Asp Lys Cys Asn His 85 <210> 113 <211> 83 <212> PRT <213> Chinese cobra <400> 113 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys His Asn Thr Gln Leu Pro Phe Ile 20 25 30 Tyr Lys Thr Cys Pro Glu Gly Lys Asn Leu Cys Phe Lys Ala Thr Leu 35 40 45 Arg Lys Phe Pro Leu Lys Phe Pro Val Lys Arg Gly Cys Ala Asp Asn 50 55 60 Cys Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Thr Asp 65 70 75 80 Lys Cys Asn <210> 114 <211> 82 <212> PRT <213> Chinese cobra <400> 114 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys His Asn Ser Pro Leu Ser Leu Val 20 25 30 Tyr Gln Thr Cys Pro Ile Gly Gln Asn Ile Cys Phe Lys Ile Asn Val 35 40 45 Lys Glu Ala Pro Ser Ile Pro Val Lys Arg Ala Cys Ala Ala Thr Cys 50 55 60 Pro Lys Ser Ser Ala Leu Val Lys Val Val Cys Cys Lys Thr Asp Lys 65 70 75 80 Cys Asn <210> 115 <211> 83 <212> PRT <213> Chinese cobra <400> 115 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys His Asn Thr Gln Leu Pro Phe Ile 20 25 30 Tyr Lys Thr Cys Pro Glu Gly Lys Asn Leu Cys Phe Lys Ala Thr Leu 35 40 45 Lys Lys Phe Pro Leu Lys Phe Pro Val Lys Arg Gly Cys Ala Asp Asn 50 55 60 Cys Pro Lys Asn Ser Ala Leu Leu Lys Tyr Val Cys Cys Ser Thr Glu 65 70 75 80 Lys Cys Asn <210> 116 <211> 86 <212> PRT <213> Chinese cobra <400> 116 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Met Val Cys Met 1 5 10 15 Asp Leu Gly Tyr Thr Thr Ile Cys Tyr Asn His Leu Ser Arg Thr Pro 20 25 30 Glu Thr Thr Glu Ile Cys Pro Asp Ser Trp Tyr Phe Cys Tyr Lys Ile 35 40 45 Ser Leu Ala Asp Gly Asn Asp Val Arg Ile Lys Arg Gly Cys Thr Phe 50 55 60 Thr Cys Pro Glu Leu Arg Pro Thr Gly Lys Tyr Val Tyr Cys Cys Arg 65 70 75 80 Arg Asp Lys Cys Asn Gln 85 <210> 117 <211> 82 <212> PRT <213> Chinese cobra <400> 117 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Lys Cys His Asn Thr Gln Leu Pro Phe Ile 20 25 30 Tyr Asn Thr Cys Pro Glu Gly Lys Asn Leu Cys Phe Lys Ala Thr Leu 35 40 45 Lys Phe Pro Leu Lys Phe Pro Val Lys Arg Gly Cys Ala Ala Thr Cys 50 55 60 Pro Arg Ser Ser Ser Leu Val Lys Val Val Cys Cys Lys Thr Asp Lys 65 70 75 80 Cys Asn <210> 118 <211> 86 <212> PRT <213> Chinese cobra <400> 118 Met Lys Thr Leu Leu Leu Ser Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Thr Cys Leu Ile Cys Pro Glu Lys Tyr Cys 20 25 30 Asn Lys Val His Thr Cys Leu Asn Gly Glu Lys Ile Cys Phe Lys Lys 35 40 45 Tyr Asp Gln Arg Lys Leu Leu Gly Lys Arg Tyr Ile Arg Gly Cys Ala 50 55 60 Asp Thr Cys Pro Val Arg Lys Pro Arg Glu Ile Val Glu Cys Cys Ser 65 70 75 80 Thr Asp Lys Cys Asn His 85 <210> 119 <211> 86 <212> PRT <213> Chinese cobra <400> 119 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Thr Cys Leu Ile Cys Pro Glu Lys Tyr Cys 20 25 30 Asn Lys Val His Thr Cys Leu Asn Gly Glu Lys Ile Cys Phe Lys Lys 35 40 45 Tyr Asp Gln Arg Lys Leu Leu Gly Lys Gly Tyr Ile Arg Gly Cys Ala 50 55 60 Asp Thr Cys Pro Lys Leu Gln Asn Arg Asp Val Ile Phe Cys Cys Ser 65 70 75 80 Thr Asp Lys Cys Asn Leu 85 <210> 120 <211> 86 <212> PRT <213> Chinese cobra <400> 120 Met Lys Thr Leu Pro Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Thr Cys Leu Asn Cys Pro Glu Met Phe Cys 20 25 30 Gly Lys Phe Gln Ile Cys Arg Asn Gly Glu Lys Ile Cys Phe Lys Lys 35 40 45 Leu His Gln Arg Arg Pro Phe Ser Leu Arg Tyr Ile Arg Gly Cys Ala 50 55 60 Ala Thr Cys Pro Gly Thr Lys Pro Arg Asp Met Val Glu Cys Cys Ser 65 70 75 80 Thr Asp Arg Cys Asn Arg 85 <210> 121 <211> 86 <212> PRT <213> Chinese cobra <400> 121 Met Lys Thr Leu Leu Leu Ser Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Leu Cys Leu Ser Asp Tyr Ser Ile Phe Ser 20 25 30 Glu Thr Ile Glu Ile Cys Pro Asp Gly His Asn Phe Cys Phe Lys Lys 35 40 45 Phe Pro Lys Gly Ile Thr Arg Leu Pro Trp Val Ile Arg Gly Cys Ala 50 55 60 Ala Thr Cys Pro Lys Ala Glu Ala Arg Val Tyr Val Asp Cys Cys Ala 65 70 75 80 Arg Asp Lys Cys Asn Arg 85 <210> 122 <211> 57 <212> PRT <213> King cobra <400> 122 Leu Ile Cys His Arg Val His Gly Leu Gln Thr Cys Glu Pro Asp Gln 1 5 10 15 Lys Phe Cys Phe Arg Lys Thr Thr Met Phe Phe Pro Asn His Pro Val 20 25 30 Leu Leu Met Gly Cys Thr Ser Ser Cys Pro Thr Glu Lys Tyr Ser Val 35 40 45 Cys Cys Ser Thr Asp Lys Cys Asn Lys 50 55 <210> 123 <211> 78 <212> PRT <213> King cobra <400> 123 Met Lys Asn Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys His Arg Val His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Asp Gln Lys Phe Cys Phe Arg Lys Thr Thr Met Phe Phe 35 40 45 Pro Asn His Pro Val Leu Leu Met Gly Cys Thr Tyr Ser Cys Pro Thr 50 55 60 Glu Lys Tyr Ser Val Cys Cys Ser Thr Asp Lys Cys Asn Lys 65 70 75 <210> 124 <211> 78 <212> PRT <213> King cobra <400> 124 Met Lys Asn Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys His Gln Arg His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Ala Gln Lys Phe Cys Phe Ala Gln Thr Val Met Pro Phe 35 40 45 Pro Asn His Pro Leu Thr Leu Met Gly Cys Thr Tyr Ser Cys Pro Thr 50 55 60 Glu Lys Asn Ala Val Cys Cys Ser Thr Asp Lys Cys Asn Arg 65 70 75 <210> 125 <211> 84 <212> PRT <213> King cobra <400> 125 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Leu Asn Thr Pro Leu Pro Leu Ile 20 25 30 Tyr Thr Thr Cys Pro Ile Gly Gln Asp Lys Cys Val Lys Met Thr Ile 35 40 45 Lys Lys Leu Pro Ser Lys Tyr Asp Val Ile Arg Gly Cys Ile Asp Ile 50 55 60 Cys Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn 65 70 75 80 Lys Cys Asn Lys <210> 126 <211> 91 <212> PRT <213> King cobra <400> 126 Met Lys Thr Leu Leu Leu Thr Leu Val Val Met Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys Phe Ile Ser Ser His Asp Ser Val 20 25 30 Thr Cys Ala Pro Gly Glu Asn Val Cys Phe Leu Lys Ser Trp Cys Asp 35 40 45 Ala Trp Cys Gly Ser Arg Gly Lys Lys Leu Ser Phe Gly Cys Ala Ala 50 55 60 Thr Cys Pro Lys Val Asn Pro Gly Ile Asp Ile Glu Cys Cys Ser Thr 65 70 75 80 Asp Asn Cys Asn Pro His Pro Lys Leu Arg Pro 85 90 <210> 127 <211> 78 <212> PRT <213> King cobra <400> 127 Met Lys Thr Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys His Gln Leu His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Ala Gln Lys Phe Cys Gln Lys Arg Thr Thr Met Phe Phe 35 40 45 Pro Asn His Pro Val Leu Leu Met Gly Cys Thr Tyr Asn Cys Pro Thr 50 55 60 Glu Arg Tyr Ser Val Cys Cys Ser Thr Asp Lys Cys Asn Lys 65 70 75 <210> 128 <211> 78 <212> PRT <213> King cobra <400> 128 Met Lys Thr Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys His Arg Val His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Asp Gln Lys Phe Cys Phe Arg Lys Thr Thr Met Phe Phe 35 40 45 Pro Asn His Pro Val Leu Leu Met Gly Cys Thr Tyr Ser Cys Pro Thr 50 55 60 Glu Lys Tyr Ser Val Cys Cys Ser Thr Asp Lys Cys Asn Lys 65 70 75 <210> 129 <211> 78 <212> PRT <213> King cobra <400> 129 Met Lys Asn Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys His Gln Val His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Ala Gln Lys Phe Cys Gln Ile Arg Thr Thr Met Phe Phe 35 40 45 Pro Asn His Pro Val Leu Leu Met Gly Cys Thr Tyr Asn Cys Pro Thr 50 55 60 Glu Arg Tyr Ser Val Cys Cys Ser Thr Asp Lys Cys Asn Lys 65 70 75 <210> 130 <211> 77 <212> PRT <213> King cobra <400> 130 Met Lys Asn Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys Asn Arg Val His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Ala His Lys Phe Cys Phe Ser Lys Thr Val Met Pro Phe 35 40 45 Pro Asn His Pro Leu Thr Leu Met Gly Cys Thr Tyr Ser Cys Pro Thr 50 55 60 Glu Arg Asn Ala Val Cys Cys Ser Thr Asp Lys Cys Asn 65 70 75 <210> 131 <211> 78 <212> PRT <213> King cobra <400> 131 Met Lys Thr Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys His Gln Leu His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Ala Gln Lys Phe Cys Gln Lys Arg Thr Thr Met Phe Ser 35 40 45 Pro Asn His Pro Val Leu Leu Met Gly Cys Thr Tyr Asn Cys Pro Thr 50 55 60 Glu Arg Tyr Ser Val Cys Cys Ser Thr Asp Lys Cys Asn Lys 65 70 75 <210> 132 <211> 78 <212> PRT <213> King cobra <400> 132 Met Lys Thr Leu Leu Leu Thr Phe Leu Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys His Gln Val His Gly Leu Gln Thr 20 25 30 Cys Glu Pro Ala Gln Lys Phe Cys Gln Lys Arg Thr Thr Met Phe Phe 35 40 45 Pro Asn His Pro Val Leu Leu Met Gly Cys Thr Tyr Asn Cys Pro Thr 50 55 60 Glu Arg Tyr Ser Val Cys Cys Ser Thr Asp Lys Cys Asn Lys 65 70 75 <210> 133 <211> 86 <212> PRT <213> King cobra <400> 133 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Tyr Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Asn His Gln Ser Thr Thr Pro 20 25 30 Glu Thr Thr Glu Ile Cys Pro Asp Ser Gly Tyr Phe Cys Tyr Lys Ser 35 40 45 Ser Trp Ile Asp Gly Arg Glu Gly Arg Ile Glu Arg Gly Cys Thr Phe 50 55 60 Thr Cys Pro Glu Leu Thr Pro Asn Gly Lys Tyr Val Tyr Cys Cys Arg 65 70 75 80 Arg Asp Lys Cys Asn Gln 85 <210> 134 <211> 83 <212> PRT <213> King cobra <400> 134 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Ser Leu Ile Cys Phe Asn Gln Glu Thr Tyr Arg Pro 20 25 30 Glu Thr Thr Thr Thr Cys Pro Asp Gly Glu Asp Thr Cys Tyr Ser Thr 35 40 45 Phe Trp Asn Asp His Arg Gly Val Lys Ile Glu Arg Gly Cys Gly Cys 50 55 60 Pro Arg Val Asn Pro Gly Ile Ser Ile Ile Cys Cys Lys Thr Asp Lys 65 70 75 80 Cys Asn Asn <210> 135 <211> 93 <212> PRT <213> King cobra <400> 135 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Val Thr Pro Asp Val Lys Ser 20 25 30 Glu Thr Cys Pro Ala Gly Gln Asp Ile Cys Tyr Thr Glu Thr Trp Cys 35 40 45 Asp Ala Trp Cys Thr Ser Arg Gly Lys Arg Val Asn Leu Gly Cys Ala 50 55 60 Ala Thr Cys Pro Ile Val Lys Pro Gly Val Glu Ile Lys Cys Cys Ser 65 70 75 80 Thr Asp Asn Cys Asn Pro Phe Pro Thr Arg Lys Arg Pro 85 90 <210> 136 <211> 94 <212> PRT <213> King cobra <400> 136 Met Lys Ile Leu Leu Leu Thr Leu Val Val Val Thr Ile Met Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Lys Thr Gly Glu Arg Ile Ile 20 25 30 Ser Glu Thr Cys Pro Pro Gly Gln Asp Leu Cys Tyr Met Lys Thr Trp 35 40 45 Cys Asp Val Phe Cys Gly Ser Arg Gly Arg Val Ile Glu Leu Gly Cys 50 55 60 Thr Ala Thr Cys Pro Thr Val Lys Pro His Glu Gln Ile Thr Cys Cys 65 70 75 80 Ser Thr Asp Asn Cys Asn Pro His Pro Lys Met Lys Gln Arg 85 90 <210> 137 <211> 83 <212> PRT <213> King cobra <400> 137 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Ser Leu Ile Cys Phe Asn Gln Glu Thr Tyr Arg Pro 20 25 30 Glu Thr Thr Thr Thr Cys Pro Asp Gly Glu Asp Thr Cys Tyr Ser Thr 35 40 45 Phe Trp Asn Asp His His Gly Val Lys Ile Glu Arg Gly Cys Gly Cys 50 55 60 Pro Arg Val Asn Pro Pro Ile Ser Ile Ile Cys Cys Lys Thr Asp Lys 65 70 75 80 Cys Asn Asn <210> 138 <211> 73 <212> PRT <213> King cobra <400> 138 Thr Lys Cys Tyr Val Thr Pro Asp Ala Thr Ser Gln Thr Cys Pro Asp 1 5 10 15 Gly Gln Asp Ile Cys Tyr Thr Lys Thr Trp Cys Asp Gly Phe Cys Ser 20 25 30 Ser Arg Gly Lys Arg Ile Asp Leu Gly Cys Ala Ala Thr Cys Pro Lys 35 40 45 Val Lys Pro Gly Val Asp Ile Lys Cys Cys Ser Thr Asp Asn Cys Asn 50 55 60 Pro Phe Pro Thr Trp Lys Arg Lys His 65 70 <210> 139 <211> 90 <212> PRT <213> King cobra <400> 139 Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Leu Cys Leu Asp 1 5 10 15 Leu Gly Tyr Thr Thr Lys Cys Tyr Ile Thr Pro Asp Val Lys Ser Glu 20 25 30 Thr Cys Pro Asp Gly Glu Asn Ile Cys Tyr Thr Lys Thr Trp Cys Asp 35 40 45 Val Trp Cys Gly Ser Arg Gly Arg Arg Val Asp Leu Gly Cys Ala Ala 50 55 60 Thr Cys Pro Ile Val Lys Pro Gly Val Asn Ile Asn Cys Cys Ser Thr 65 70 75 80 Asp Asn Cys Asn Pro Phe Pro Lys Arg Ser 85 90 <210> 140 <211> 91 <212> PRT <213> King cobra <400> 140 Met Lys Thr Leu Leu Leu Thr Leu Val Val Met Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Ser Leu Ile Cys Phe Ile Ser Pro His Asp Ser Val 20 25 30 Thr Cys Ala Pro Gly Glu Asn Val Cys Phe Leu Lys Ser Trp Cys Asp 35 40 45 Ala Trp Cys Gly Ser Arg Gly Lys Lys Leu Ser Phe Gly Cys Ala Ala 50 55 60 Thr Cys Pro Lys Val Asn Pro Gly Ile Asp Ile Glu Cys Cys Ser Thr 65 70 75 80 Asp Asn Cys Asn Pro His Pro Lys Leu Arg Pro 85 90 <210> 141 <211> 73 <212> PRT <213> King cobra <400> 141 Thr Lys Cys Tyr Val Thr Pro Asp Val Lys Ser Glu Thr Cys Pro Ala 1 5 10 15 Gly Gln Asp Ile Cys Tyr Thr Glu Thr Trp Cys Asp Ala Trp Cys Thr 20 25 30 Ser Arg Gly Lys Arg Val Asp Leu Gly Cys Ala Ala Thr Cys Pro Ile 35 40 45 Val Lys Pro Gly Val Glu Ile Lys Cys Cys Ser Thr Asp Asn Cys Asn 50 55 60 Pro Phe Pro Thr Trp Arg Lys Arg Pro 65 70 <210> 142 <211> 72 <212> PRT <213> King cobra <400> 142 Thr Lys Cys Tyr Lys Thr Gly Asp Arg Ile Ile Ser Glu Ala Cys Pro 1 5 10 15 Pro Gly Gln Asp Leu Cys Tyr Met Lys Thr Trp Cys Asp Val Phe Cys 20 25 30 Gly Thr Arg Gly Arg Val Ile Glu Leu Gly Cys Thr Ala Thr Cys Pro 35 40 45 Thr Val Lys Pro His Glu Gln Ile Thr Cys Cys Ser Thr Asp Asn Cys 50 55 60 Asp Pro His His Lys Met Leu Gln 65 70 <210> 143 <211> 72 <212> PRT <213> King cobra <400> 143 Thr Lys Cys Tyr Ile Thr Pro Asp Val Lys Ser Glu Thr Cys Pro Asp 1 5 10 15 Gly Glu Asn Ile Cys Tyr Thr Lys Ser Trp Cys Asp Val Phe Cys Thr 20 25 30 Ser Arg Gly Lys Arg Ile Asp Leu Gly Cys Ala Ala Thr Cys Pro Lys 35 40 45 Val Lys Pro Gly Val Asp Ile Lys Cys Cys Ser Thr Asp Asn Cys Asn 50 55 60 Pro Phe Thr Pro Trp Lys Arg His 65 70 <210> 144 <211> 86 <212> PRT <213> King cobra <400> 144 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly His Thr Leu Ile Cys Val Lys Gln Tyr Thr Ile Phe Gly 20 25 30 Val Thr Pro Glu Ile Cys Ala Asp Gly Gln Asn Leu Cys Tyr Lys Thr 35 40 45 Trp His Met Val Tyr Pro Gly Gly Tyr Asp His Thr Arg Gly Cys Ala 50 55 60 Ala Thr Cys Pro Lys Met Lys Asn His Asp Thr Val His Cys Cys Thr 65 70 75 80 Thr Asp Lys Cys Asn Leu 85 <210> 145 <211> 73 <212> PRT <213> King cobra <400> 145 Thr Lys Cys Tyr Val Thr Pro Asp Val Lys Ser Glu Thr Cys Pro Ala 1 5 10 15 Gly Gln Asp Leu Cys Tyr Thr Glu Thr Trp Cys Val Ala Trp Cys Thr 20 25 30 Val Arg Gly Lys Arg Val Ser Leu Thr Cys Ala Ala Ile Cys Pro Ile 35 40 45 Val Pro Pro Lys Val Ser Ile Lys Cys Cys Ser Thr Asp Ala Cys Gly 50 55 60 Pro Phe Pro Thr Trp Pro Asn Val Arg 65 70 <210> 146 <211> 86 <212> PRT <213> King cobra <400> 146 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Leu Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Thr Cys Leu Thr His Glu Ser Leu Phe Phe 20 25 30 Glu Thr Thr Glu Thr Cys Ser Asp Gly Gln Asn Leu Cys Tyr Ala Lys 35 40 45 Trp Phe Ala Val Phe Pro Gly Ala Arg Arg Pro Asp Gly Gly Cys Ala 50 55 60 Ala Thr Cys Pro Asp Lys Val Pro Leu Glu Ile Val Asn Cys Cys Thr 65 70 75 80 Thr Asp Lys Cys Asn Leu 85 <210> 147 <211> 86 <212> PRT <213> King cobra <400> 147 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Met Thr Cys Tyr Thr Gln Tyr Ser Leu Ser Pro 20 25 30 Pro Thr Thr Lys Thr Cys Pro Asp Gly Gln Asn Leu Cys Tyr Lys Arg 35 40 45 Trp Phe Ala Phe Ile Pro His Gly Asn Lys Phe Phe Arg Gly Cys Ala 50 55 60 Ala Ala Cys Pro Lys Ala Glu His Asn Glu Val Val Arg Cys Cys Ala 65 70 75 80 Arg Asp Lys Cys Asn Leu 85 <210> 148 <211> 84 <212> PRT <213> King cobra <400> 148 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Leu Asn Thr Pro Leu Pro Leu Ile 20 25 30 Tyr Lys Thr Cys Pro Ile Gly Gln Asp Lys Cys Ile Lys Met Thr Ile 35 40 45 Lys Lys Leu Pro Ser Lys Tyr Asp Val Ile Arg Gly Cys Ile Asp Ile 50 55 60 Cys Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn 65 70 75 80 Lys Cys Asn Lys <210> 149 <211> 84 <212> PRT <213> King cobra <400> 149 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Leu Asn Thr Pro Leu Pro Leu Ile 20 25 30 Tyr Lys Thr Cys Pro Ile Gly Gln Asp Arg Cys Ile Lys Met Thr Ile 35 40 45 Lys Lys Leu Pro Ser Lys Tyr Asp Val Ile Arg Gly Cys Ile Asp Ile 50 55 60 Cys Pro Lys Ser Ser Ala Asp Val Glu Val Leu Cys Cys Asp Thr Asn 65 70 75 80 Lys Cys Asn Lys <210> 150 <211> 93 <212> PRT <213> King cobra <400> 150 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Leu Cys Tyr Lys Thr Pro Ser Pro Ile Asn 20 25 30 Ala Glu Thr Cys Pro Pro Gly Glu Asn Leu Cys Tyr Thr Lys Met Trp 35 40 45 Cys Asp Ala Trp Cys Ser Ser Arg Gly Lys Val Ile Glu Leu Gly Cys 50 55 60 Ala Ala Thr Cys Pro Ser Lys Lys Pro Tyr Glu Glu Val Asp Cys Cys 65 70 75 80 Ser Thr Asp Asn Cys Asn Pro His Pro Lys Leu Arg Pro 85 90 <210> 151 <211> 91 <212> PRT <213> King cobra <400> 151 Met Lys Thr Leu Leu Leu Thr Leu Val Val Met Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Leu Ile Cys Phe Ile Ser Ser His Asp Ser Val 20 25 30 Thr Cys Ala Pro Gly Glu Asn Val Cys Phe Leu Lys Ser Trp Cys Asp 35 40 45 Ala Trp Cys Gly Ser Arg Gly Lys Lys Leu Ser Phe Gly Cys Ala Ala 50 55 60 Thr Cys Pro Arg Val Asn Pro Gly Ile Asp Ile Glu Cys Cys Ser Thr 65 70 75 80 Asp Asn Cys Asn Pro His Pro Lys Leu Arg Pro 85 90 <210> 152 <211> 91 <212> PRT <213> King cobra <400> 152 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Met Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Val Thr Pro Asp Val Thr Ser 20 25 30 Gln Thr Cys Pro Asp Gly Gln Asn Ile Cys Tyr Thr Glu Thr Trp Cys 35 40 45 Asp Ala Trp Cys Gly Ser Arg Gly Lys Arg Val Asn Leu Gly Cys Ala 50 55 60 Ala Thr Cys Pro Lys Val Asn Pro Gly Val Asp Ile Ile Cys Cys Ser 65 70 75 80 Thr Asp Asn Cys Asn Pro Phe Pro Lys Arg Ser 85 90 <210> 153 <211> 93 <212> PRT <213> King cobra <400> 153 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Val Thr Pro Asp Val Lys Ser 20 25 30 Glu Thr Cys Pro Asp Gly Glu Asn Ile Cys Tyr Thr Lys Ser Trp Cys 35 40 45 Glu Val Phe Cys Thr Ser Arg Gly Lys Arg Ile Asp Leu Gly Arg Ala 50 55 60 Ala Thr Cys Pro Lys Val Lys Pro Gly Val Asp Ile Lys Cys Cys Ser 65 70 75 80 Thr Asp Asn Cys Asn Pro Phe Thr Pro Trp Lys Arg His 85 90 <210> 154 <211> 86 <212> PRT <213> King cobra <400> 154 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Ser Leu Thr Cys Leu Asn Cys Pro Glu Gln Tyr Cys 20 25 30 Lys Arg Ile His Thr Cys Arg Asn Gly Glu Asn Val Cys Phe Lys Arg 35 40 45 Phe Tyr Glu Gly Lys Leu Leu Cys Lys Gln Phe Arg Arg Gly Cys Ala 50 55 60 Ala Thr Cys Pro Glu Ala Lys Ser Arg Glu Ile Val Gln Cys Cys Ser 65 70 75 80 Thr Asp Glu Cys Asn His 85 <210> 155 <211> 83 <212> PRT <213> King cobra <400> 155 Met Lys Pro Val Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Ile Cys Leu Lys Gln Glu Pro Phe Gln Pro 20 25 30 Glu Thr Thr Thr Thr Cys Pro Glu Gly Glu Asp Ala Cys Tyr Asn Leu 35 40 45 Phe Trp Ser Asp His Ser Glu Ile Lys Ile Glu Met Gly Cys Gly Cys 50 55 60 Pro Lys Thr Glu Pro Tyr Thr Asn Leu Tyr Cys Cys Lys Ile Asp Ser 65 70 75 80 Cys Asn Lys <210> 156 <211> 84 <212> PRT <213> King cobra <400> 156 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Leu Asn Thr Pro Leu Pro Leu Ile 20 25 30 Tyr Thr Thr Cys Pro Ile Gly Gln Asp Lys Cys Val Lys Met Thr Ile 35 40 45 Lys Lys Leu Pro Ser Lys Tyr Asp Val Ile Arg Gly Cys Thr Asp Ile 50 55 60 Cys Pro Lys Ser Ser Ala Asp Val Val Val Val Cys Cys Asp Thr Asn 65 70 75 80 Lys Cys Asp Lys <210> 157 <211> 84 <212> PRT <213> King cobra <400> 157 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Leu Asn Thr Pro Leu Pro Leu Ile 20 25 30 Tyr Lys Thr Cys Pro Ile Gly Gln Asp Lys Cys Ile Lys Met Thr Ile 35 40 45 Lys Lys Leu Pro Ser Lys Tyr Asp Val Ile Arg Gly Cys Thr Asp Ile 50 55 60 Cys Pro Lys Ser Ser Ala Asp Val Val Val Val Cys Cys Asp Thr Asn 65 70 75 80 Lys Cys Asn Lys <210> 158 <211> 72 <212> PRT <213> King cobra <400> 158 Thr Lys Cys Tyr Lys Thr Gly Asp Arg Ile Ile Ser Glu Ala Cys Pro 1 5 10 15 Pro Gly Gln Asp Leu Cys Tyr Met Lys Thr Trp Cys Asp Val Phe Cys 20 25 30 Gly Thr Arg Gly Arg Val Ile Glu Leu Gly Cys Thr Ala Thr Cys Pro 35 40 45 Thr Val Lys Pro His Glu Gln Ile Thr Cys Cys Ser Thr Asp Asn Cys 50 55 60 Asn Pro His Pro Lys Met Lys Gln 65 70 <210> 159 <211> 84 <212> PRT <213> King cobra <400> 159 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Lys Cys Leu Asn Thr Pro Leu Pro Leu Ile 20 25 30 Tyr Thr Thr Cys Pro Ile Gly Gln Asp Lys Cys Val Lys Met Thr Ile 35 40 45 Lys Lys Leu Pro Ser Lys Tyr Asp Val Ile Arg Gly Cys Thr Asp Ile 50 55 60 Cys Pro Lys Ser Ser Ala Asp Val Val Val Val Cys Cys Asp Thr Asn 65 70 75 80 Lys Cys Asn Lys <210> 160 <211> 94 <212> PRT <213> King cobra <400> 160 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Leu Cys Leu 1 5 10 15 Asp Leu Gly Leu Glu Leu Thr Asn Ala Pro Asp Ser Trp Ser Ser Arg 20 25 30 Arg Thr Cys Leu Cys Pro Ala Trp Val Pro Leu Arg Ser Arg Pro Val 35 40 45 Ala Gly His Ser Lys Gln Cys Gly Ser Arg Gly Arg Arg Val Asp Leu 50 55 60 Gly Cys Ala Ala Thr Cys Pro Ile Val Lys Pro Gly Val Asn Ile Asn 65 70 75 80 Cys Cys Ser Thr Asp Asn Cys Asn Pro Phe Pro Lys Arg Ser 85 90 <210> 161 <211> 93 <212> PRT <213> King cobra <400> 161 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Val Thr Pro Asp Ala Thr Ser 20 25 30 Gln Thr Cys Pro Asp Gly Glu Asn Ile Cys Tyr Thr Lys Ser Trp Cys 35 40 45 Asp Val Phe Cys Ser Ser Arg Gly Lys Arg Ile Asp Leu Gly Cys Ala 50 55 60 Ala Thr Cys Pro Lys Val Lys Pro Gly Val Asp Ile Lys Cys Cys Ser 65 70 75 80 Thr Asp Asn Cys Asn Pro Phe Thr Pro Trp Lys Arg His 85 90 <210> 162 <211> 94 <212> PRT <213> King cobra <400> 162 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Met Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Lys Thr Gly Glu Arg Ile Ile 20 25 30 Ser Glu Thr Cys Pro Pro Gly Gln Asp Leu Cys Tyr Met Lys Thr Trp 35 40 45 Cys Asp Val Phe Cys Gly Ser Arg Gly Arg Val Ile Glu Leu Gly Cys 50 55 60 Thr Ala Thr Cys Pro Thr Val Lys His His Glu Gln Ile Thr Cys Cys 65 70 75 80 Ser Thr Asp Asn Cys Asn Pro His Pro Lys Met Lys Gln Arg 85 90 <210> 163 <211> 94 <212> PRT <213> King cobra <400> 163 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Met Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Thr Lys Cys Tyr Lys Thr Gly Glu Arg Ile Ile 20 25 30 Ser Glu Thr Cys Pro Pro Gly Gln Asp Leu Cys Tyr Met Lys Thr Trp 35 40 45 Cys Asp Val Phe Cys Gly Ser Arg Gly Arg Val Val Glu Leu Gly Cys 50 55 60 Thr Ala Thr Cys Pro Thr Val Lys Pro His Glu Gln Ile Thr Cys Cys 65 70 75 80 Ser Thr Asp Asn Cys Asn Pro His Pro Lys Met Lys Gln Arg 85 90 <210> 164 <211> 91 <212> PRT <213> King cobra <400> 164 Met Lys Thr Leu Leu Leu Thr Leu Val Val Val Thr Ile Val Cys Leu 1 5 10 15 Asp Leu Gly Tyr Thr Arg Ile Cys His Lys Ser Ser Phe Ile Ser Glu 20 25 30 Thr Cys Pro Asp Gly Gln Asn Leu Cys Tyr Leu Lys Ser Trp Cys Asp 35 40 45 Ile Phe Cys Gly Ser Arg Gly Glu Arg Leu Glu Phe Gly Cys Ala Ala 50 55 60 Thr Cys Pro Glu Val Lys Pro Gly Val Asn Ile Glu Cys Cys Ser Thr 65 70 75 80 Asp Asn Cys Asn Pro His Pro Lys Leu Arg Pro 85 90 <210> 165 <211> 81 <212> PRT <213> King cobra <400> 165 Leu Thr Leu Val Val Val Thr Ile Val Cys Leu Asp Leu Gly Tyr Thr 1 5 10 15 Leu Thr Cys Leu Ile Cys Pro Glu Glu Tyr Cys Lys Arg Ile His Thr 20 25 30 Cys Arg Asp Gly Glu Asn Val Cys Phe Lys Gly Phe Tyr Glu Gly Lys 35 40 45 Gln Leu Gly Lys Gln Phe Arg Arg Gly Cys Ala Ala Thr Cys Pro Glu 50 55 60 Gly Lys Pro Asn Glu Ile Val Gln Cys Cys Ser Thr Asp Glu Cys Asn 65 70 75 80 His
Claims
1. A snake venom antigenic epitope chimera, characterized in that, The amino acid sequence of the chimera is set forth in SEQ ID NO:
39. The amino acid sequence of the chimera is set forth in SEQ ID NO: 39.
Citation Information
Patent Citations
A fully humanized bispecific anti-tetanus antibody, its construction method and application
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HTNV epitope linear consecutive polypeptide and epitope peptide-compound tetramer and application
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