Structural highlights
Publication Abstract from PubMed
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.
Insights into the mechanism of drug resistance: X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex.,Liu Z, Yedidi RS, Wang Y, Dewdney TG, Reiter SJ, Brunzelle JS, Kovari IA, Kovari LC Biochem Biophys Res Commun. 2013 Jan 8. pii: S0006-291X(13)00021-1. doi:, 10.1016/j.bbrc.2012.12.127. PMID:23313846[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu Z, Yedidi RS, Wang Y, Dewdney TG, Reiter SJ, Brunzelle JS, Kovari IA, Kovari LC. Insights into the mechanism of drug resistance: X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex. Biochem Biophys Res Commun. 2013 Jan 8. pii: S0006-291X(13)00021-1. doi:, 10.1016/j.bbrc.2012.12.127. PMID:23313846 doi:http://dx.doi.org/10.1016/j.bbrc.2012.12.127
