Because of the increased appearance of vancomycin resistance in methicillin-resistant Staphylococcus aureus, and its consequences to hospital patients, it is of vital importance to understand the nature of this resistance and to develop effective inhibitors for treatment of infections. Vancomycin is used as the backup antibiotic for gram-positive infections which do not respond to penicillin therapy and for patients allegeric to penicillin.
Four specific aims are proposed: (1) determine x-ray structure of the Leuconostoc mesenteroides D-Ala:D-Lactate ligase, (2) determine the structure of F261Y mutant which exhibits a reversal of substrate specificity to produce D-alanine-D-alanine, (3) to generate a model of VanA, and (4) inhibitor design.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034330-05
Application #
2871515
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Tseng, Christopher K
Project Start
1998-02-01
Project End
2001-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269