5UPZ

HIV-1 wild Type protease with GRL-0518A , an isophthalamide-derived P2-P3 ligand with the para-hydoxymethyl sulfonamide isostere as the P2' group

5UPZ の概要

• エントリーDOI: 10.2210/pdb5upz/pdb
• 関連するPDBエントリー: 5ULT 5UOV
• 分子名称: Protease, N~3~-{(2S,3R)-3-hydroxy-4-[{[4-(hydroxymethyl)phenyl]sulfonyl}(2-methylpropyl)amino]-1-phenylbutan-2-yl}-N~1~-methyl-N~1~-[(4-methyl-1,3-oxazol-2-yl)methyl]benzene-1,3-dicarboxamide, SODIUM ION, ... (6 entities in total)
• 機能のキーワード: an isophthalamide-derived p2-p3 ligand, hiv-1 protease inhibitor grl-0518a, darunavir, multidrug-resistant, hydrolase inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22480.68

構造登録者

Wang, Y.-F.,Agniswamy, J.,Weber, I.T. (登録日: 2017-02-05, 公開日: 2017-05-10, 最終更新日: 2023-10-04)

主引用文献

Ghosh, A.K.,Brindisi, M.,Nyalapatla, P.R.,Takayama, J.,Ella-Menye, J.R.,Yashchuk, S.,Agniswamy, J.,Wang, Y.F.,Aoki, M.,Amano, M.,Weber, I.T.,Mitsuya, H.
Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex.
Bioorg. Med. Chem., 25:5114-5127, 2017

PubMed Abstract: Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme K of 0.025nM and antiviral IC of 69nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27Å resolution. These structures revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site.

PubMed: 28434781
DOI: 10.1016/j.bmc.2017.04.005

実験手法

X-RAY DIFFRACTION (1.27 Å)