4L1A

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

Summary for 4L1A

• Entry DOI: 10.2210/pdb4l1a/pdb
• Descriptor: 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)
• Functional Keywords: hiv-1 protease, multi-drug resistance, ic50, lopinavir, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 2
• Total formula weight: 22170.04

Authors

Liu, Z.,Yedidi, R.S.,Wang, Y.,Dewdney, T.,Reiter, S.,Brunzelle, J.,Kovari, I.,Kovari, L. (deposition date: 2013-06-03, release date: 2014-04-02, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)