Crystal structure of the class D beta-lactamase OXA-10.
We report the crystal structure of a class D beta-lactamase, the broad spectrum enzyme OXA-10 from Pseudomonas aeruginosa at 2.0 A 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 mediated formation of a homodimer. Kinetic and hydrodynamic data shows that the dimer is a relevant species in solution and is the more active form of the enzyme. 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 counterpart in OXA-10 to the residues proposed to act as general bases in either 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 hydrolysis. Clinical variants of OXA-10 are also discussed in light of the structure.
Paetzel
M
M
Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3, Canada.
Danel
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F
de Castro
L
L
Mosimann
S C
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Page
M G
MG
Strynadka
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D000595:Amino Acid Sequence; D001665:Binding Sites; D019281:Dimerization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C055187:beta-lactamase PSE-2; D001618:beta-Lactamases