3HVT

STRUCTURAL BASIS OF ASYMMETRY IN THE HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 REVERSE TRANSCRIPTASE HETERODIMER

「2HVT」から置き換えられました 「1HVT」から置き換えられました

3HVT の概要

• エントリーDOI: 10.2210/pdb3hvt/pdb
• 分子名称: HIV-1 REVERSE TRANSCRIPTASE (SUBUNIT P66), HIV-1 REVERSE TRANSCRIPTASE (SUBUNIT P51), 11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B:2',3'-E][1,4]DIAZEPIN-6-ONE (3 entities in total)
• 機能のキーワード: nucleotidyltransferase
• 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): P03366 P03366
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 114326.18

構造登録者

Steitz, T.A.,Smerdon, S.J.,Jaeger, J.,Wang, J.,Kohlstaedt, L.A.,Chirino, A.J.,Friedman, J.M.,Rice, P.A. (登録日: 1994-07-25, 公開日: 1994-10-15, 最終更新日: 2024-02-21)

主引用文献

Smerdon, S.J.,Jager, J.,Wang, J.,Kohlstaedt, L.A.,Chirino, A.J.,Friedman, J.M.,Rice, P.A.,Steitz, T.A.
Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1.
Proc.Natl.Acad.Sci.Usa, 91:3911-3915, 1994

PubMed Abstract: The dipyridodiazepinone Nevirapine is a potent and highly specific inhibitor of the reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1). It is a member of an important class of nonnucleoside drugs that appear to share part or all of the same binding site on the enzyme but are susceptible to a variety of spontaneous drug-resistance mutations. The co-crystal-structure of HIV-1 RT and Nevirapine has been solved previously at 3.5-A resolution and now is partially refined against data extending to 2.9-A spacing. The drug is bound in a hydrophobic pocket and in contact with some 38 protein atoms from the p66 palm and thumb subdomains. Most, but not all, nonnucleoside drug-resistance mutations map to residues in close contact with Nevirapine. The major effects of these mutations are to introduce steric clashes with the drug molecule or to remove favorable protein-drug contacts. Additionally, four residues (Phe-227, Trp-229, Leu-234, and Tyr-319) in contact with Nevirapine have not been selected as sites of drug-resistance mutations, implying that there may be limitations on the number and types of resistance mutations that yield viable virus. Strategies of inhibitor design that target interactions with these conserved residues may yield drugs that are less vulnerable to escape mutations.

PubMed: 7513427
DOI: 10.1073/pnas.91.9.3911

実験手法

X-RAY DIFFRACTION (2.9 Å)