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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
7R01CA052047-08
Application #
2894833
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Cole, John S
Project Start
1992-07-01
Project End
2001-04-30
Budget Start
1999-07-01
Budget End
2000-04-30
Support Year
8
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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