Beta-lactamase enzyme (serine-type and metallo-beta-lactamase) (Beta-lactamase (BLA); serine-β-lactamase (SBL); metallo-β-lactamase (MBL))

Beta-lactamase enzymes are bacterial enzymes that confer resistance to beta-lactam antibiotics by hydrolyzing the antibiotic’s beta-lactam ring, rendering the drug inactive[1][4][5][6]. There are two major molecular classes: - Serine-type beta-lactamases (SBLs): Utilize a nucleophilic serine residue to form an acyl-enzyme intermediate with the beta-lactam substrate, resulting in hydrolysis[1][3][4]. - Metallo-beta-lactamases (MBLs): Employ zinc ions at the active site to activate a water molecule, which attacks the beta-lactam ring to facilitate hydrolysis without covalent intermediate formation[4][5][6]. Both SBLs and MBLs are highly diverse, distributed across bacterial chromosomes and plasmids, and together provide broad-spectrum antibiotic resistance, threatening global health[1][5][6]. Clinical and developmental inhibitors—such as cyclic boronates and N-sulfamoyl compounds—target these enzymes by mimicking native reaction intermediates, with some acting against both SBLs and MBLs[2][5][6].

Other names

Serine beta-lactamaseMetallo-beta-lactamaseSBLMBLBLA

Enzymatic hydrolysis of beta-lactam ring via nucleophilic attack (serine or zinc-activated water)[1][3][4][6] Inhibitors act as transition state analogs mimicking the hydrolytic intermediate[2][5][6] Inhibition of beta-lactamase activity, restoring antibiotic efficacy[5][6]