1C1C

CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH TNK-6123

1C1C の概要

• エントリーDOI: 10.2210/pdb1c1c/pdb
• 関連するPDBエントリー: 1C0T 1C0U 1C1B 1KLM 1REV 1RT1 1RT2 1RT3 1RT4 1RT5 1RT6 1RT7 1RTH 1RTI 1RTJ 1RTV 1VRU
• 分子名称: HIV-1 REVERSE TRANSCRIPTASE (A-CHAIN), HIV-1 REVERSE TRANSCRIPTASE (B-CHAIN), 6-(cyclohexylsulfanyl)-1-(ethoxymethyl)-5-(1-methylethyl)pyrimidine-2,4(1H,3H)-dione, ... (4 entities in total)
• 機能のキーワード: hiv-1 reverse transcriptase, aids, non-nucleoside inhibitor, drug design, transferase
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• 細胞内の位置: Matrix protein p17: Virion . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585 P04585
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 116320.45

構造登録者

Hopkins, A.L.,Ren, J.,Tanaka, H.,Baba, M.,Okamato, M.,Stuart, D.I.,Stammers, D.K. (登録日: 1999-07-21, 公開日: 2000-07-21, 最終更新日: 2024-11-20)

主引用文献

Hopkins, A.L.,Ren, J.,Tanaka, H.,Baba, M.,Okamato, M.,Stuart, D.I.,Stammers, D.K.
Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants.
J.Med.Chem., 42:4500-4505, 1999

PubMed Abstract: Two analogues of the nonnucleoside inhibitor of HIV-1 RT, MKC-442 (emivirine), containing different C6 substituents have been designed to be less susceptible to the commonly found drug-resistance mutation of Tyr181Cys. Compound TNK-6123 had a C6 thiocyclohexyl group designed to have more flexibility in adapting to the mutated drug-binding site. GCA-186 had additional 3',5'-dimethyl substituents aimed at forming close contacts with the conserved residue Trp229. Both compounds showed approximately 30-fold greater inhibitory effect than MKC-442 to the Tyr181Cys mutant virus as well as to the clinically important Lys103Asn virus. X-ray crystallographic structure determination of complexes with HIV-1 RT confirmed the predicted binding modes. These strategies might be used to improve the resilience of other NNRTI series against common drug-resistance mutations.

PubMed: 10579814
DOI: 10.1021/jm990192c

実験手法

X-RAY DIFFRACTION (2.5 Å)