4EYR

Crystal structure of multidrug-resistant clinical isolate 769 HIV-1 protease in complex with ritonavir

4EYR の概要

• エントリーDOI: 10.2210/pdb4eyr/pdb
• 関連するPDBエントリー: 1TW7 3OQ7
• 関連するBIRD辞書のPRD_ID: PRD_001001
• 分子名称: HIV-1 PROTEASE, RITONAVIR (3 entities in total)
• 機能のキーワード: protease, 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: 22260.21

構造登録者

Liu, Z.,Yedidi, R.S.,Wang, Y.,Brunzelle, J.S.,Kovari, I.A.,Kovari, L.C. (登録日: 2012-05-01, 公開日: 2013-01-30, 最終更新日: 2024-02-28)

主引用文献

Liu, Z.,Yedidi, R.S.,Wang, Y.,Dewdney, T.G.,Reiter, S.J.,Brunzelle, J.S.,Kovari, I.A.,Kovari, L.C.
Insights into the mechanism of drug resistance: X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex.
Biochem.Biophys.Res.Commun., 431:232-238, 2013

PubMed Abstract: Ritonavir (RTV) is a first generation HIV-1 protease inhibitor with rapidly emerging drug resistance. Mutations at residues 46, 54, 82 and 84 render the HIV-1 protease drug resistant against RTV. We report the crystal structure of multi-drug resistant (MDR) 769 HIV-1 protease (carrying resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84 and 90) complexed with RTV and the in vitro enzymatic IC(50) of RTV against MDR HIV-1 protease. The structural and functional studies demonstrate significant drug resistance of MDR HIV-1 protease against RTV, arising from reduced hydrogen bonds and Van der Waals interactions between RTV and MDR HIV-1 protease.

PubMed: 23313846
DOI: 10.1016/j.bbrc.2012.12.127

実験手法

X-RAY DIFFRACTION (1.8 Å)