4L1A

Crystallographic study of multi-drug resistant HIV-1 protease Lopinavir complex: mechanism of drug recognition and resistance

4L1A の概要

• エントリーDOI: 10.2210/pdb4l1a/pdb
• 分子名称: MDR769 HIV-1 protease, N-{1-BENZYL-4-[2-(2,6-DIMETHYL-PHENOXY)-ACETYLAMINO]-3-HYDROXY-5-PHENYL-PENTYL}-3-METHYL-2-(2-OXO-TETRAHYDRO-PYRIMIDIN-1-YL)-BUTYRAMIDE, ... (4 entities in total)
• 機能のキーワード: hiv-1 protease, multi-drug resistance, ic50, lopinavir, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22170.04

構造登録者

Liu, Z.,Yedidi, R.S.,Wang, Y.,Dewdney, T.,Reiter, S.,Brunzelle, J.,Kovari, I.,Kovari, L. (登録日: 2013-06-03, 公開日: 2014-04-02, 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.
Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance.
Biochem.Biophys.Res.Commun., 437:199-204, 2013

PubMed Abstract: Lopinavir (LPV) is a second generation HIV-1 protease inhibitor. Drug resistance has rapidly emerged against LPV since its US FDA approval on September 15, 2000. Mutations at residues 32I, L33F, 46I, 47A, I54V, V82A, I84V, and L90M render the protease drug resistant against LPV. We report the crystal structure of a clinical isolate multi-drug resistant (MDR) 769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) complexed with LPV and the in vitro enzymatic IC50 of LPV against MDR 769. The structural and functional studies demonstrate significant drug resistance of MDR 769 against LPV, arising from reduced interactions between LPV and the protease target.

PubMed: 23792096
DOI: 10.1016/j.bbrc.2013.06.027

実験手法

X-RAY DIFFRACTION (1.9 Å)