6PRF

HIV-1 Protease multiple drug resistant clinical isolate mutant PR20 with GRL-14213A

6PRF の概要

• エントリーDOI: 10.2210/pdb6prf/pdb
• 関連するPDBエントリー: 3UCB 3UF3 4YHQ 6BZ2
• 分子名称: Protease, YTTRIUM ION, (3S,3aR,5R,7aS,8S)-hexahydro-4H-3,5-methanofuro[2,3-b]pyran-8-yl [(2S,3R)-4-[{[2-(cyclopropylamino)-1,3-benzothiazol-6-yl]sulfonyl}(2-methylpropyl)amino]-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl]carbamate, ... (4 entities in total)
• 機能のキーワード: protease, inhibitor, multiple mutant, viral protein complex, hydrolase, hydrolase-hydrolase inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype (HIV-1)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23040.06

構造登録者

Kneller, D.W.,Agniswamy, J.,Weber, I.T. (登録日: 2019-07-10, 公開日: 2019-09-18, 最終更新日: 2023-10-11)

主引用文献

Kneller, D.W.,Agniswamy, J.,Ghosh, A.K.,Weber, I.T.
Potent antiviral HIV-1 protease inhibitor combats highly drug resistant mutant PR20.
Biochem.Biophys.Res.Commun., 519:61-66, 2019

PubMed Abstract: Drug-resistance threatens effective treatment of HIV/AIDS. Clinical inhibitors, including darunavir (1), are ineffective for highly resistant protease mutant PR20, however, antiviral compound 2 derived from 1 with fused tricyclic group at P2, extended amino-benzothiazole P2' ligand and two fluorine atoms on P1 shows 16-fold better inhibition of PR20 enzyme activity. Crystal structures of PR20 and wild-type PR complexes reveal how the extra groups of 2 counteract the expanded ligand-binding pocket, dynamic flaps, and faster dimer dissociation of PR20.

PubMed: 31474336
DOI: 10.1016/j.bbrc.2019.08.126

実験手法

X-RAY DIFFRACTION (1.21 Å)