Protein-protein interactions: mechanisms and modification by drugs

被引:78
|
作者
Veselovsky, AV
Ivanov, YD
Ivanov, AS
Archakov, AI
Lewi, P
Janssen, P
机构
[1] Russian Acad Med Sci, Inst Biomed Chem, Moscow 119992, Russia
[2] Janssen Pharmaceut NY, Ctr Mol Design, Beerse, Belgium
关键词
protein-protein interaction; protein surface; inhibitors; drug design; antagonist; protein complex; thermodynamics; dimerization;
D O I
10.1002/jmr.597
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein-protein interactions form the proteinaceous network, which plays a central role in numerous processes in the cell. This review highlights the main structures, properties of contact surfaces, and forces involved in protein-protein interactions. The properties of protein contact surfaces depend on their functions. The characteristics of contact surfaces of short-lived protein complexes share some similarities with the active sites of enzymes. The contact surfaces of permanent complexes resemble domain contacts or the protein core. It is reasonable to consider protein-protein complex formation as a continuation of protein folding. The contact surfaces of the protein complexes have unique structure and properties, so they represent prospective targets for a new generation of drugs. During the last decade, numerous investigations have been undertaken to find or design small molecules that block protein dimerization or protein(peptide)receptor interaction, or on the other hand, induce protein dimerization. Copyright (C) 2002 John Wiley Sons, Ltd.
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页码:405 / 422
页数:20
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