Co-evolution of nelfinavir-resistant HIV-1 protease and the p1-p6 substrate
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Student Authors
Madhavi KolliUMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2006-04-10Keywords
Drug Resistance, Viral; Evolution, Molecular; Gene Products, gag; HIV Protease; HIV Protease Inhibitors; HIV-1; Humans; Nelfinavir; Substrate Specificity; gag Gene Products, Human Immunodeficiency VirusBiochemistry, Biophysics, and Structural Biology
Life Sciences
Medicine and Health Sciences
Microbiology
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Show full item recordAbstract
The selective pressure of the competitive protease inhibitors causes both HIV-1 protease and occasionally its substrates to evolve drug resistance. We hypothesize that this occurs particularly in substrates that protrude beyond the substrate envelope and contact residues that mutate in response to a particular protease inhibitor. To validate this hypothesis, we analyzed substrate and protease sequences for covariation. Using the chi2 test, we show a positive correlation between the nelfinavir-resistant D30N/N88D protease mutations and mutations at the p1-p6 cleavage site as compared to the other cleavage sites. Both nelfinavir and the substrate p1-p6 protrude beyond the substrate envelope and contact residue 30, thus possibly making the p1-p6 cleavage site more vulnerable to co-evolution.Source
Virology. 2006 Apr 10;347(2):405-9. Epub 2006 Jan 20. Link to article on publisher's siteDOI
10.1016/j.virol.2005.11.049Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33963PubMed ID
16430939Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.virol.2005.11.049