Serine beta-lactamase and Metallo-beta-lactamase

Serine beta-lactamase and metallo-beta-lactamase are two mechanistically distinct but functionally related classes of **beta-lactamase enzymes** produced by bacteria, responsible for hydrolyzing and thereby inactivating beta-lactam antibiotics such as penicillins, cephalosporins, and carbapenems[1][3][4][6]. Serine beta-lactamases (SBLs, classes A, C, and D) employ a conserved nucleophilic serine residue at their active site to catalyze hydrolysis via acylation-deacylation chemistry, whereas metallo-beta-lactamases (MBLs, class B) coordinate 1 or 2 zinc ions at the active site, with a zinc-activated water/hydroxide serving as the nucleophile for hydrolysis[1][3][4][6]. Both types are major causes of bacterial resistance to beta-lactam antibiotics. SBLs can be targeted by certain inhibitors such as clavulanic acid and avibactam, while MBLs are not susceptible to these and still lack broadly effective clinical inhibitors, though molecules like taniborbactam and N-sulfamoylpyrrole-2-carboxylates are under investigation[2][5]. These enzymes are direct targets for novel antibacterial drugs and inhibitors aimed at overcoming resistance, but differ in their structure, catalytic mechanism, and susceptibility to inhibition[1][2][4][5].

Other names

Serine β-lactamaseMetallo-β-lactamaseSBLMBLβ-lactamase

Hydrolysis and inactivation of beta-lactam antibiotics (penicillins, cephalosporins, carbapenems)\n- Inhibition by covalent or transition-state analog inhibitors (clavulanic acid, avibactam, boronates for SBLs; experimental inhibitors for MBLs)