STRUCTURE/FUNCTION COMPARISONS OF HIV 1 & RSV PROTEASES

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DESCRIPTION (Adapted from investigator's abstract): The structural information obtained through crystallographic studies on RSV and HIV-1 proteases will guide the present study in attempts to examine the role of critical residues that determine the substrate selection and catalytic efficiency. Attempts to change the specificity of one PR into the other for both heterologous and homologous substrates will be undertaken by site-directed mutagenesis and tested by biochemical characterization of purified enzymes. The effect of PR subunit symmetry for optimal catalytic efficiencies will be examined by selective mutagenesis of individual subunits of the PR homodimer. The information gathered from these experiments would be used to construct a "designer protease" to act on other than normal target sites on HIV-1 RT. Finally, altered proteases will be tested in vivo , for further understanding of their role in biological processes involved in virus assembly and reproduction.