Crystal structures of zidovudine- or lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41, 184, and 215

被引：52

作者：

Chamberlain, PP

Ren, J

Nichols, CE

Douglas, L

Lennerstrand, J

Larder, BA

Stuart, DI

Stammers, DK

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England

[2] Oxford Ctr Mol Sci, Oxford OX1 3QT, England

[3] Visible Genet, Cambridge CB4 0GA, England

来源：

JOURNAL OF VIROLOGY | 2002年 / 76卷 / 19期

关键词：

D O I：

10.1128/JVI.76.19.10015-10019.2002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Six structures of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing combinations of resistance mutations for zidovudine (AZT) (M41L and T215Y) or lamivudine (M184V) have been determined as inhibitor complexes. Minimal conformational changes in the polymerase or nonnucleoside RT inhibitor sites compared to the mutant RTMC (D67N, K70P, T215F, and K219N) are observed, indicating that such changes may occur only with certain combinations of mutations. Model building M41L and T215Y into HIV-1 RT-DNA and docking in ATP that is utilized in the pyrophosphorolysis reaction for AZT resistance indicates that some conformational rearrangement appears necessary in RT for ATP to interact simultaneously with the M41L and T215Y mutations.

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页码：10015 / 10019

页数：5

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