6DIF

Wild-type HIV-1 protease in complex with tipranavir

6DIF の概要

• エントリーDOI: 10.2210/pdb6dif/pdb
• 関連するPDBエントリー: 2IEN 6DIL 6DJ1 6DJ2
• 分子名称: HIV-1 protease, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: antiviral agents, protein-inhibitor structures, hiv drug resistance, 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: 22489.65

構造登録者

Wong-Sam, A.E.,Wang, Y.-F.,Weber, I.T. (登録日: 2018-05-23, 公開日: 2018-10-17, 最終更新日: 2023-10-11)

主引用文献

Wong-Sam, A.,Wang, Y.F.,Zhang, Y.,Ghosh, A.K.,Harrison, R.W.,Weber, I.T.
Drug Resistance Mutation L76V Alters Nonpolar Interactions at the Flap-Core Interface of HIV-1 Protease.
ACS Omega, 3:12132-12140, 2018

PubMed Abstract: Four HIV-1 protease (PR) inhibitors, clinical inhibitors lopinavir and tipranavir, and two investigational compounds and , were studied for their effect on the structure and activity of PR with drug-resistant mutation L76V (PR). Compound exhibited the best value of 1.9 nM for PR, whereas the other three inhibitors had values of 4.5-7.6 nM, 2-3 orders of magnitude worse than for wild-type enzymes. Crystal structures showed only minor differences in interactions of inhibitors with PR compared to wild-type complexes. The shorter side chain of Val76 in the mutant lost hydrophobic interactions with Lys45 and Ile47 in the flap, and with Asp30 and Thr74 in the protein core, consistent with decreased stability. Inhibitors forming additional polar interactions with the flaps or dimer interface of PR were unable to compensate for the decrease in internal hydrophobic contacts. These structures provide insights for inhibitor design.

PubMed: 30288468
DOI: 10.1021/acsomega.8b01683

実験手法

X-RAY DIFFRACTION (1.2 Å)