Comparison of the specificity of homo- and heterodimeric linked HIV-1 and HIV-2 proteinase dimers.
The specificity of linked homo- and heterodimeric HIV-1 and HIV-2 proteinases was characterized by using oligopeptide substrates. For two substrates the k(cat)/Km values for the heterodimers were the mean values for those of the homodimers, suggesting that these substrates could productively bind into the heterodimers in both directions. However, for two other substrates the k(cat)/Km values for the heterodimers were higher than those of the homodimers, suggesting that these substrates could productively bind into the enzymes in a preferable direction. However, the mode of binding does not seem to depend on the sequential position of the subunits. The studied linked homo- and heterodimers may represent intermediate stages in the evolution of bilobal aspartic proteinases. As divergence in sequence of the two halves of such a proteinase increases, the possibility of bidirectional binding is likely lost at the expense of the optimized side-chain subsite interactions. The differences in observed and calculated k(cat)/Km values revealed dependence of the substrate specificity at one subsite of the enzyme from the next residue in sequence of substrate. These findings were also supported by molecular modeling studies.
Bagossi
P
P
Department of Biochemistry and Molecular Biology, University Medical School of Debrecen, Hungary.
Cheng
Y S
YS
Oroszlan
S
S
Tözsér
J
J
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D002213:Capsid / Q000378:metabolism; D019281:Dimerization; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics; D014763:Viral Matrix Proteins / Q000378:metabolism
D009842:Oligopeptides; D014763:Viral Matrix Proteins; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2