STRUCTURAL BASIS OF DRUG-RESISTANCE FOR THE V82A MUTANT OF HIV-1 PROTEINASE

被引：100

作者：

BALDWIN, ET ^{[1
]}

BHAT, TN ^{[1
]}

LIU, BS ^{[1
]}

PATTABIRAMAN, N ^{[1
]}

ERICKSON, JW ^{[1
]}

机构：

[1] NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PRO,FREDERICK,MD 21702

来源：

NATURE STRUCTURAL BIOLOGY | 1995年 / 2卷 / 03期

关键词：

D O I：

10.1038/nsb0395-244

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：

A major problem in the development of antiviral therapies for AIDS has keen the emergence of drug resistance, We report an analysis of the structure of a Val 82 to Ala mutant of HIV-1 proteinase complexed to A-77003, a C2 symmetry-based inhibitor, Modelling studies predicted that the V82A mutation would result in decreased van der Waals' interactions with the phenyl rings of A-77003 in both S1 and S1(1) subsites, Unexpected rearrangements of the protein backbone, however, resulted in favourable re-packing of inhibitor and enzyme atoms in the S1 but not the S1(1) subsite. This analysis reveals the importance of enzyme flexibility in accommodating alternate packing arrangements, and can be applied to the re-design of inhibitors targeted to drug resistant variants which emerge in the clinic.

引用

页码：244 / 249

页数：6

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