Serine beta-lactamase class D (OXA-type beta-lactamase)

Class D serine beta-lactamases (often termed OXA-type beta-lactamases) are bacterial enzymes that hydrolyze the amide bond of the beta-lactam ring in penicillins, cephalosporins, cephamycins, monobactams, and for some variants carbapenems, thereby inactivating these antibiotics and conferring resistance. They belong to the serine beta-lactamase superfamily (Ambler molecular class D) that uses an active-site serine for catalysis and are grouped functionally within group 2 serine beta-lactamases alongside class A enzymes. Structural studies of a prototypical member, OXA-10, show an alpha/beta fold related to classes A and C but with distinct active-site features and catalytic base arrangement, indicating a mechanistically distinct serine-dependent hydrolysis pathway within class D. These enzymes likely evolved from DD-transpeptidases (penicillin-binding proteins), the native targets of beta-lactam antibiotics, and enable bacteria—often Gram-negative species that can secrete these enzymes—to survive beta-lactam exposure, driving clinically significant antimicrobial resistance.

Other names

Class D beta-lactamaseOXA beta-lactamaseOXA-type serine beta-lactamaseClass D serine beta-lactamase

Serine-dependent hydrolysis: formation of an acyl-enzyme intermediate via active-site serine followed by deacylation to open the beta-lactam ring and inactivate the antibiotic. Distinct class D catalytic features: class D enzymes share the alpha/beta fold with classes A and C but employ a distinct catalytic base arrangement; structural studies (e.g., OXA-10) indicate differences from class A (Glu166) and class C (Tyr150) general base roles, implying a distinct catalytic mechanism within serine beta-lactamases.