Structural characterization of the interactions of optimized product inhibitors with the N-terminal proteinase domain of the hepatitis C virus (HCV) NS3 protein by NMR and modelling studies

被引：57

作者：

Cicero, DO ^{[1
]}

Barbato, G ^{[1
]}

Koch, U ^{[1
]}

Ingallinella, P ^{[1
]}

Bianchi, E ^{[1
]}

Nardi, MC ^{[1
]}

Steinkühler, C ^{[1
]}

Cortese, R ^{[1
]}

Matassa, V ^{[1
]}

De Francesco, R ^{[1
]}

Pessi, A ^{[1
]}

Bazzo, R ^{[1
]}

机构：

[1] Ist Ric Biol Mol P Angeletti, I-00040 Pomezia, Italy

来源：

JOURNAL OF MOLECULAR BIOLOGY | 1999年 / 289卷 / 02期

关键词：

HCV; NS3-proteinase; inhibitors; binding; NR IR;

D O I：

10.1006/jmbi.1999.2746

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：

The interactions of peptide inhibitors, obtained by the optimization of N-terminal cleavage products of natural substrates, with the protease of human hepatitis C virus (HCV) are characterized by NMR and modelling studies. The S-binding region of the enzyme and the bound conformation of the ligands are experimentally determined. The NMR data are then used as the experimental basis for modelling studies of the structure of the complex. The S-binding region involves the loop connecting strands E2 and F2, and appears shallow and solvent-exposed. The ligand binds in an extended conformation, forming an antiparallel beta-sheet with strand E2 of the protein, with the P1 carboxylate group in the oxyanion hole. (C) 1999 Academic Press.

引用

页码：385 / 396

页数：12

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