We plan to determine the crystallographic structure of the OXA-1 oxacillinase, a troublesome bacterial beta-lactamase which provides clinical resistance to beta-lactam antibiotics (penicillins and cephalosporins). A member of the less-characterized class D family of serine beta-lactamases, OXA-1 is especially active against the penicillins oxacillin and cloxacillin and is now found in 10 percent of E. coli clinical isolates. The architecture of the beta-lactam hydrolysis site in OXA-1 will be compared with that in a class A penicillinase and a class C cephalosporinase to understand the preferential ability of OXA-1 to hydrolyze oxacillin and cloxacillin. Because the oxacillinases are poorly inhibited by currently used agents such as clavulanic acid, a crystallographic structure will aid in the design of more effective inhibitors. OXA-1 crystals which diffract to very high resolution (1.5 A) have been examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI052216-01
Application #
6499694
Study Section
Physical Biochemistry Study Section (PB)
Project Start
2002-07-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$84,523
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