Class A serine β-lactamase (Class A β-lactamase)

Class A serine β-lactamase is a bacterial enzyme that represents the most widespread antibiotic resistance mechanism against β-lactam drugs, including penicillins and cephalosporins.[2] These enzymes function as serine-dependent hydrolases that catalyze the breakdown of β-lactam antibiotics through formation of an acyl-enzyme intermediate, utilizing conserved amino acid residues including Ser70 (catalytic residue), Glu166, and Asn170 located on the characteristic omega (Ω) loop structure.[1][3][4] Class A β-lactamases evolved from penicillin-binding proteins (PBPs) through the formation of the Ω-loop, which enables more efficient deacylation and inactivation of antibiotics compared to the original transpeptidase targets.[1] Common variants include TEM-1 (the most frequently encountered), CTX-M enzymes (extended-spectrum variants), and KPC enzymes (carbapenem-hydrolyzing variants).[3][4] As a therapeutic target, inhibiting Class A β-lactamases is critical for restoring the efficacy of β-lactam antibiotics against resistant bacterial pathogens; current approaches include mechanism-based inhibitors like clavulanate and emerging boronic acid-based non-β-lactam inhibitors designed through structure-based drug design.[2]

Other names

Serine β-lactamase class ATEM β-lactamase (for the TEM-1 representative enzyme)CTX-M β-lactamase (for extended-spectrum variants)KPC β-lactamase (for carbapenem-hydrolyzing variants)Penicillinaseβ-lactam hydrolase (serine-dependent)

Serine-dependent hydrolysis of β-lactam antibiotics through acyl-enzyme intermediate formation[6] Active site catalysis utilizing conserved Ser70 residue[3] Deacylation via Glu166 and Asn170 residues located on the omega (Ω) loop[1][4] Faster hydrolysis and inactivation of β-lactams compared to inhibition by penicillin-binding proteins (PBPs)[1] Formation of tetrahedral geometry at boron atoms in boronic acid complexes for inhibitor binding[2]