2QD8

HIV-1 Protease Mutant I84V with potent Antiviral inhibitor GRL-98065

2QD8 の概要

• エントリーDOI: 10.2210/pdb2qd8/pdb
• 関連するPDBエントリー: 2QCI 2QD6 2QD7 2Z4O
• 分子名称: Protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: hiv-1 protease mutant i84v, protease inhibitor, hydrolase
• 由来する生物種: Human immunodeficiency virus 1
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane ; Lipid-anchor. Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P03367
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22241.94

構造登録者

Wang, Y.F.,Tie, Y.,Boross, P.I.,Tozser, J.,Ghosh, A.K.,Harrison, R.W.,Weber, I.T. (登録日: 2007-06-20, 公開日: 2008-04-22, 最終更新日: 2023-10-25)

主引用文献

Wang, Y.F.,Tie, Y.,Boross, P.I.,Tozser, J.,Ghosh, A.K.,Harrison, R.W.,Weber, I.T.
Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease.
J.Med.Chem., 50:4509-4515, 2007

PubMed Abstract: The potent new antiviral inhibitor GRL-98065 (1) of HIV-1 protease (PR) has been studied with PR variants containing the single mutations D30N, I50V, V82A, and I84V that provide resistance to the major clinical inhibitors. Compound 1 had inhibition constants of 17-fold, 8-fold, 3-fold, and 3-fold, respectively, for PR(D30N), PR(I50V), PR(V82A), and PR(I84V) relative to wild type PR. The chemically related darunavir had similar relative inhibition, except for PR(D30N), where inhibitor 1 was approximately 3-fold less potent. The high resolution (1.11-1.60 Angstrom) crystal structures of PR mutant complexes with inhibitor 1 showed small changes relative to the wild type enzyme. PR(D30N) and PR(V82A) showed compensating interactions with inhibitor 1 relative to those of PR, while reduced hydrophobic contacts were observed with PR(I50V) and PR(I84V). Importantly, inhibitor 1 complexes showed fewer changes relative to wild type enzyme than reported for darunavir complexes. Therefore, inhibitor 1 is a valuable addition to the antiviral inhibitors with high potency against resistant strains of HIV.

PubMed: 17696515
DOI: 10.1021/jm070482q

実験手法

X-RAY DIFFRACTION (1.35 Å)