Crystal structure of the class D beta-lactamase OXA-10

We report the crystal structure of a class D beta-lactamase, the broad spec trum enzyme OXA-10 from Pseudomonas aeruginosa at 2.0 Angstrom resolution. There are significant differences between the overall fold observed in this structure and those of the evolutionarily related class A and class C beta -lactamases. Furthermore, the structure suggests the unique, cation mediate d formation of a homodimer, Kinetic and hydrodynamic data shows that the di mer is a relevant species in solution and is the more active form of the en zyme. Comparison of the molecular details of the active sites of the class A and class C enzymes with the OXA-10 structure reveals that there is no co unterpart in OXA-10 to the residues proposed to act as general bases in eit her of these enzymes (Glu 166 and Tyr 150. respectively). Our structures of the native and chloride inhibited forms of OXA-10 suggest that the class D enzymes have evolved a distinct catalytic mechanism for beta-lactam hydrol ysis, Clinical variants of OXA-10 are also discussed in light of the struct ure.