3QAA

HIV-1 wild type protease with a substituted bis-Tetrahydrofuran inhibitor, GRL-044-10A

3QAA の概要

• エントリーDOI: 10.2210/pdb3qaa/pdb
• 関連するPDBエントリー: 2IEN 3OK9
• 分子名称: HIV-1 Protease, (3R,3aS,4R,6aR)-4-methoxyhexahydrofuro[2,3-b]furan-3-yl [(2S,3R)-3-hydroxy-4-{[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino}-1-phenylbutan-2-yl]carbamate, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: aspartic acid protease, hiv-1 protease inhibitor grl-044-10a, substituted bis-tetrahydrofuran inhibitor, wild-type hiv-1 protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 1 (HIV-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 : P03366
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22444.23

構造登録者

Wang, Y.-F.,Agniswamy, J.,Weber, I.T. (登録日: 2011-01-10, 公開日: 2011-12-21, 最終更新日: 2023-09-13)

主引用文献

Ghosh, A.K.,Martyr, C.D.,Steffey, M.,Wang, Y.F.,Agniswamy, J.,Amano, M.,Weber, I.T.,Mitsuya, H.
Design of substituted bis-Tetrahydrofuran (bis-THF)-derived Potent HIV-1 Protease Inhibitors, Protein-ligand X-ray Structure, and Convenient Syntheses of bis-THF and Substituted bis-THF Ligands.
ACS Med Chem Lett, 2:298-302, 2011

PubMed Abstract: We investigated substituted bis-THF-derived HIV-1 protease inhibitors in order to enhance ligand-binding site interactions in the HIV-1 protease active site. In this context, we have carried out convenient syntheses of optically active bis-THF and C4-substituted bis-THF ligands using a [2,3]-sigmatropic rearrangement as the key step. The synthesis provided convenient access to a number of substituted bis-THF derivatives. Incorporation of these ligands led to a series of potent HIV-1 protease inhibitors. Inhibitor 23c turned out to be the most potent (K(i) = 2.9 pM; IC(50) = 2.4 nM) among the inhibitors. An X-ray structure of 23c-bound HIV-1 protease showed extensive interactions of the inhibitor with the protease active site, including a unique water-mediated hydrogen bond to the Gly-48 amide NH in the S2 site.

PubMed: 22509432

実験手法

X-RAY DIFFRACTION (1.4 Å)