Serine β-lactamase and Metallo-β-lactamase

Serine β-lactamase and metallo-β-lactamase are two principal classes of β-lactamase enzymes responsible for bacterial resistance to β-lactam antibiotics—including penicillins, cephalosporins, carbapenems, and others. Serine β-lactamases (SBLs; Ambler classes A, C, D) utilize a nucleophilic serine residue in their active site to catalyze the hydrolysis of the β-lactam ring via a serine-bound acyl intermediate[1][3]. Metallo-β-lactamases (MBLs; Ambler class B) use one or two zinc ions to stabilize a hydroxide nucleophile that attacks the β-lactam ring, operating through a different, non-covalent mechanism and hydrolyzing a broader range of β-lactam antibiotics, notably carbapenems[3][4][6]. These enzymes are widely distributed in Gram-negative (and some Gram-positive) bacteria and represent a major mechanism of clinical antibiotic resistance[1][3]. Therapeutic strategies include inhibitors targeting serine β-lactamases (e.g., clavulanic acid, avibactam) and newer agents in clinical development that inhibit both SBL and MBL types (e.g., cyclic boronates like taniborbactam and QPX7728)[2][5][6]. Accurate detection of these enzymes in pathogens serves as an important biomarker for antibiotic selection, while their rapid evolution and dissemination present major safety and public health challenges[1][3][6].

Other names

Serine beta-lactamaseSBLMetallo-beta-lactamaseMBLβ-lactamase

Beta-lactamase inhibition, Formation of acyl-enzyme intermediates (SBL), Disruption of zinc-coordination and inhibition (MBL), Transition state analogue inhibition