Class A serine beta-lactamase (SBL (class A))

Class A serine β-lactamases are serine-active-site hydrolases that catalyze hydrolysis of the endocyclic amide of β-lactam antibiotics through a conserved two-step mechanism: acylation of the catalytic Ser70 to form an acyl-enzyme intermediate, followed by deacylation driven by a strategically positioned, activated water coordinated by residues including Glu166 and Asn170 in the Ω-loop and oxyanion-hole interactions from Ser70/Ala237 main-chain NHs. They are a major functional group (Ambler Class A; Bush functional group 2) that includes broad-spectrum enzymes, extended-spectrum β-lactamases (ESBLs) such as TEM and CTX-M, and Class A serine carbapenemases like KPC, collectively driving β-lactam resistance in clinical Gram-negative pathogens and some Gram-positive bacteria.

Other names

Class A β-lactamaseSerine β-lactamase (class A)ESBLs (extended-spectrum β-lactamases; subset within Class A such as TEM/CTX-M variants)TEM β-lactamase family (e.g., TEM-1, extended-spectrum TEM)CTX-M β-lactamasesKPC carbapenemase (Klebsiella pneumoniae carbapenemase; Class A serine carbapenemase)

For β-lactam antibiotics: enzyme-mediated hydrolysis of the β-lactam ring via a two-step serine mechanism (acylation by active-site Ser70, then deacylation by an activated water), inactivating the antibiotic For β-lactamase inhibitors: mechanism-based covalent acylation and/or reversible covalent inhibition that blocks the catalytic serine and prevents hydrolysis of co-administered β-lactams (general to Class A inhibitor profiles)