4EYR

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

Summary for 4EYR

• Entry DOI: 10.2210/pdb4eyr/pdb
• Related: 1TW7 3OQ7
• Related PRD ID: PRD_001001
• Descriptor: HIV-1 PROTEASE, RITONAVIR (3 entities in total)
• Functional Keywords: protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 2
• Total formula weight: 22260.21

Authors

Liu, Z.,Yedidi, R.S.,Wang, Y.,Brunzelle, J.S.,Kovari, I.A.,Kovari, L.C. (deposition date: 2012-05-01, release date: 2013-01-30, 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.
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

Experimental method

X-RAY DIFFRACTION (1.8 Å)