4EYR : Crystal structure of multidrug-resistant clinical isolate 769 HIV-1 protease in complex with ritonavir

  • Ravikiran S. Yedidi (Contributor)
  • Zhigang Liu (Contributor)
  • Iulia A. Kovari (Contributor)
  • Ladislau C. Kovari (Contributor)
  • Yong Wang (Contributor)
  • Joseph S. Brunzelle (Contributor)



Experimental Technique/Method:X-RAY DIFFRACTION
Release Date:2013-01-30
Deposition Date:2012-05-01
Revision Date:2013-02-27
Molecular Weight:22260.21
Macromolecule Type:Protein
Residue Count:198
Atom Site Count:1564

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.
Date made available2013

Cite this