This Article Full Text (PDF) Other Versions of this Article: JVI.00726-08v1 82/22/11476    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Mosebi, S. Articles by Sayed, Y. PubMed PubMed Citation Articles by Mosebi, S. Articles by Sayed, Y.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.00726-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Active Site Mutations in the South African HIV-1 Subtype C Protease Impact Significantly on Clinical Inhibitor Binding: a Kinetic and Thermodynamic Study

Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of the Witwatersrand, I Jan Smuts Avenue, Johannesburg, 2050, South Africa; AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Johannesburg, South Africa

^* To whom correspondence should be addressed. Email: yasien.sayed{at}wits.ac.za.

	Abstract

HIV in sub-Saharan Africa represents about 56 % of global infections. Active site mutations (V82A and V82F/I84V) in the less studied South African HIV-1 subtype C protease indicated that neither mutation impacted significantly on proteolytic functioning of the protease. However, the binding affinity and inhibition by saquinavir, ritonavir, indinavir and nelfinavir was weaker for each variant when compared with the wild-type protease with the double mutant exhibiting the most dramatic change. Therefore, our results show that the C-SA V82F/I84V double mutation decreased the binding affinity of protease inhibitors to levels significantly lower than required for effective inhibition.