COMPARISON OF THE SPECIFICITY OF HOMODIMERIC AND HETERODIMERIC LINKEDHIV-1 AND HIV-2 PROTEINASE DIMERS

The specificity of linked homo- and heterodimeric HIV-1 and HIV-2 prot einases was characterized by using oligopeptide substrates, For two su bstrates the k(cat)/K-m values for the heterodimers were the mean valu es 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)/K-m values for the heterodimers we re higher than those of the homodimers, suggesting that these substrat es could productively bind into the enzymes in a preferable direction. However, the mode of binding does not seem to depend on the sequentia l 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 pr oteinase 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)/K-m values revealed dependence of the substrate specificity at one subsite of the enzyme from the next residue in sequence of substrate. These findings were al so supported by molecular modeling studies.