1RT3

AZT DRUG RESISTANT HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH 1051U91

1RT3 の概要

• エントリーDOI: 10.2210/pdb1rt3/pdb
• 分子名称: HIV-1 REVERSE TRANSCRIPTASE, 6,11-DIHYDRO-11-ETHYL-6-METHYL-9-NITRO-5H-PYRIDO[2,3-B][1,5]BENZODIAZEPIN-5-ONE (3 entities in total)
• 機能のキーワード: nucleotidyltransferase, hiv-1 reverse transcriptase, aids, nucleoside inhibitor, drug resistance mutation
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P04585 P04585
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116391.37

構造登録者

Ren, J.,Stammers, D.K.,Stuart, D.I. (登録日: 1998-06-29, 公開日: 1999-02-16, 最終更新日: 2023-08-09)

主引用文献

Ren, J.,Esnouf, R.M.,Hopkins, A.L.,Jones, E.Y.,Kirby, I.,Keeling, J.,Ross, C.K.,Larder, B.A.,Stuart, D.I.,Stammers, D.K.
3'-Azido-3'-deoxythymidine drug resistance mutations in HIV-1 reverse transcriptase can induce long range conformational changes.
Proc.Natl.Acad.Sci.USA, 95:9518-9523, 1998

PubMed Abstract: HIV reverse transcriptase (RT) is one of the main targets for the action of anti-AIDS drugs. Many of these drugs [e.g., 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI)] are analogues of the nucleoside substrates used by the HIV RT. One of the main problems in anti-HIV therapy is the selection of a mutant virus with reduced drug sensitivity. Drug resistance in HIV is generated for nucleoside analogue inhibitors by mutations in HIV RT. However, most of these mutations are situated some distance from the polymerase active site, giving rise to questions concerning the mechanism of resistance. To understand the possible structural bases for this, the crystal structures of AZT- and ddI-resistant RTs have been determined. For the ddI-resistant RT with a mutation at residue 74, no significant conformational changes were observed for the p66 subunit. In contrast, for the AZT-resistant RT (RTMC) bearing four mutations, two of these (at 215 and 219) give rise to a conformational change that propagates to the active site aspartate residues. Thus, these drug resistance mutations produce an effect at the RT polymerase site mediated simply by the protein. It is likely that such long-range effects could represent a common mechanism for generating drug resistance in other systems.

PubMed: 9689112
DOI: 10.1073/pnas.95.16.9518

実験手法

X-RAY DIFFRACTION (3 Å)