X-ray structure of HIV-1 protease in situ product complex

被引：11

作者：

Bihani, Subhash ^{[1
]}

Das, Amit ^{[1
]}

Prashar, Vishal ^{[1
]}

Ferrer, J. -L. ^{[2
]}

Hosur, M. V. ^{[1
]}

机构：

[1] Bhabha Atom Res Ctr, Div Solid State Phys, Bombay 400085, Maharashtra, India

[2] UJF, CNRS, CEA, Inst Biol Struct,GSY,LCCP, F-38027 Grenoble 1, France

来源：

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS | 2009年 / 74卷 / 03期

关键词：

HIV-1; protease; transition state; reaction intermediate; catalysis; inhibitor; X-ray crystallography; BARRIER HYDROGEN-BOND; IMMUNODEFICIENCY-VIRUS PROTEASE; CATALYTIC MECHANISM; AB-INITIO; CRYSTAL-STRUCTURES; ELUCIDATE DETAILS; RESOLUTION;

D O I：

10.1002/prot.22174

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：

HIV-1 protease is an effective target for design of different types of drugs against AIDS. HIV-1 protease is also one of the few enzymes that can cleave substrates containing both proline and nonproline residues at the cleavage site. We report here the first structure of HIV-1 protease complexed with the product peptides SQNY and PIV derived by in situ cleavage of the oligopeptide substrate SQNYPIV, within the crystals. In the structure, refined against 2.0-A resolution synchrotron data, a carboxyl oxygen of SQNY is hydrogen-bonded with the N-terminal nitrogen atom of PIV. At the same time, this proline nitrogen atom does not form any hydrogen bond with catalytic aspartates. These two observations suggest that the protonation of scissile nitrogen, during peptide bond cleavage, is by a gem-hydroxyl of the tetrahedral intermediate rather than by a catalytic aspartic acid.

引用

页码：594 / 602

页数：9

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