A kinetic model for comparing proteolytic processing activity and inhibitor resistance potential of mutant HIV-1 proteases.
A kinetic model is presented for the comparison of potential proteolytic processing activities of wild-type and mutant human immunodeficiency virus proteases in the presence and absence of protease inhibitors. The protease processing of gag substrate in the immature virions is assessed by the kinetic parameters, kcat, Km and Ki. The relationship of the estimated potential processing activities to the viability of the HIV mutants and their tendencies to resist inhibitors also are discussed. A fully developed model has the potential to stimulate the results of inhibitor resistance either in vivo or in cell culture.
Tang
J
J
Protein Studies Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Hartsuck
J A
JA
D004352:Drug Resistance, Microbial; D015683:Gene Products, gag / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D007700:Kinetics; D009154:Mutation; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D015683:Gene Products, gag; D017320:HIV Protease Inhibitors; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D016333:HIV Protease