Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavir.
Darunavir, a potent antiviral drug, showed an unusual second binding site on the HIV-1 protease dimer surface of the V32I drug resistant mutant and normal binding in the active site cavity. Kinetic analysis for wild type and mutant protease showed mixed-type competitive-uncompetitive inhibition for darunavir and the chemically related amprenavir, while saquinavir showed competitive inhibition. The inhibition model is consistent with the observed second binding site for darunavir and helps to explain its antiviral potency.
Kovalevsky
Andrey Y
AY
Departments of Biology and Chemistry, Molecular Basis of Disease Program, Georgia State University, Atlanta, Georgia 30303, USA.
Ghosh
Arun K
AK
Weber
Irene T
IT
D001665:Binding Sites; D002219:Carbamates / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D000069454:Darunavir; D005663:Furans; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D000069454:Darunavir