Topoisomerase enzymes control the supercoiled state of DNA and are involved in biological processes such as DNA replication and transcription. Vaccinia virus topoisomerase (VT) is a protypical type Ib enzyme closely related to human topoisomerase I (anti-cancer target). Specific peptide inhibitors of VT activity will be isolated. These inhibitors will aid in understanding the catalytic mechanism and the nature of topoisomerase inhibition. The inhibitor peptides will be identified biochemically for their ability to inhibit VT binding, cleavage and religation of their DNA substrate and tested for anti-viral activity, targeting VT using an in vivo model. Inhibitors will be further characterized using mutant VT enzymes (with defined point mutations), highlighting residues involved in enzyme activity that are affected by the inhibitory peptide. Furthermore, regions of VT that interact with the peptides will be identified by peptide-enzyme crosslinking. Finally, the inhibitory effects resulting in DNA conformational changes will be identified by DNA footprinting.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM065685-03
Application #
6730536
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Tompkins, Laurie
Project Start
2002-05-01
Project End
2004-10-31
Budget Start
2004-05-01
Budget End
2004-10-31
Support Year
3
Fiscal Year
2004
Total Cost
$24,464
Indirect Cost
Name
San Diego State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
073371346
City
San Diego
State
CA
Country
United States
Zip Code
92182