CD147 Extracellular Region 3D Structure Determination

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Solution Overview

Problem

Current methods lack a comprehensive understanding of the three-dimensional structure of CD147 extracellular region and its active sites, hindering the development of effective treatments and diagnostics for diseases such as liver cancer, as well as the design of inhibitors to regulate tumorigenesis and inflammation.

Innovation Solution

Determination of the 3D structure of the CD147 extracellular region using X-ray diffraction and computational molecular modeling, allowing for the identification of active sites and the design of inhibitors, antibodies, or small molecules that can bind to CD147, thereby inhibiting its biological activities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If the 3D structure of CD147 extracellular region is determined using X-ray diffraction and computational modeling, then the understanding of its active sites and binding mechanisms is improved, but the complexity of the research process and resource requirements increase

Engineering Contradiction:
Improveunderstanding of 3D structure and active sitesVSAvoidcomplexity of structural determination process
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The patent segments the CD147 protein into its extracellular region for crystallization and structural analysis, separating this functional domain from the transmembrane and intracellular regions. This segmentation enables focused structural determination of the active sites while simplifying the overall research process by concentrating on a specific functional portion of the protein.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs computational molecular modeling as an intermediary tool to bridge the gap between the experimentally determined crystal structure and the functional understanding of active sites. This computational intermediary enables prediction and identification of binding mechanisms without requiring additional complex experimental procedures.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If inhibitors are designed based on the determined 3D structure, then the effectiveness of treating diseases such as liver cancer is improved, but the time and resources required for drug development increase

Engineering Contradiction:
Improveeffectiveness of disease treatmentVSAvoidtime for drug development
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent performs preliminary structural determination and active site identification through X-ray diffraction and computational modeling before initiating drug design. This preliminary action establishes the structural foundation and binding mechanisms in advance, enabling subsequent inhibitor design to proceed more efficiently with reduced time and resource requirements.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent utilizes computational methods to simulate and analyze various binding parameters and interaction modes between potential inhibitors and the CD147 active sites. By changing and optimizing these parameters in silico, the patent identifies promising inhibitor candidates that can be rapidly transitioned to experimental validation, accelerating the overall drug development process.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If computational molecular modeling is used to identify binding sites and design inhibitors, then the precision of target engagement is improved, but the computational resources and expertise required increase

Engineering Contradiction:
Improveprecision of binding site identificationVSAvoidcomputational resources consumed
Core Design Contradiction:
Measurement precisionVSUse of energy by moving object

Solution Approach 1:

The patent applies computational molecular modeling to a limited but critical extent - specifically for analyzing the crystal structure and identifying active sites in the extracellular region. This partial application of computational methods provides sufficient precision for binding site identification without requiring excessive computational resources for the entire protein structure or all possible binding modes.

Inventive Principle:
Principle #16Partial or excessive action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables structure-based drug design for regulating tumorigenesis, tumor metastasis, inflammation, and viral infection, providing a foundation for developing therapeutic agents that can effectively target CD147, enhancing treatment options for liver cancer and other conditions.

Implementation Method 1

Determination of the 3D structure of the CD147 extracellular region using X-ray diffraction

Methodology Applied
Scientific EffectX-ray diffraction: Diffraction

Data Source

PatentEP2194065B1Crystal structure of CD147 extracellular region and use thereof
Publication Date: 2014.05.07 CHEN ZHI NAN
  • EP2194065B1 patent drawingFigure 1
  • EP2194065B1 patent drawingFigure 2A~2B
  • EP2194065B1 patent drawingFigure 3~4

AI summary

A crystal, a preparation method and 3D structure of CD147 extracellular region are provided. Such 3D structure is useful in the determination of the active site of CD147 extracellular region by computer modeling or molecular docking method. The crystal and/or 3D structure are useful in a structure-based drug design and the selection of an antibody, a ligand or an interacting molecule of CD 147 extracellular region.