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.
| Sun, Tao; Bethel, Christopher R; Bonomo, Robert A et al. (2004) Inhibitor-resistant class A beta-lactamases: consequences of the Ser130-to-Gly mutation seen in Apo and tazobactam structures of the SHV-1 variant. Biochemistry 43:14111-7 |
| Sun, Tao; Nukaga, Michiyoshi; Mayama, Kayoko et al. (2003) Comparison of beta-lactamases of classes A and D: 1.5-A crystallographic structure of the class D OXA-1 oxacillinase. Protein Sci 12:82-91 |
