Class C β-lactamase (AmpC)

Class C β-lactamase, also known as AmpC or cephalosporinase, is a serine-dependent enzyme produced by various bacteria, primarily Gram-negative Proteobacteria such as Escherichia, Klebsiella, Pseudomonas, and Acinetobacter, that hydrolyzes the β-lactam ring in antibiotics like cephalosporins, rendering them ineffective against penicillin-binding proteins (PBPs). It features conserved catalytic motifs including 64SXSK, 150YXN, and 315KTG, with a structure comprising two mixed α/β domains and key loops (Ω-loop and R2-loop) that facilitate substrate binding and catalysis. These enzymes contribute to widespread antibiotic resistance, particularly in infections caused by Enterobacterales and Pseudomonadales, by conferring resistance to β-lactam antibiotics including extended-spectrum cephalosporins when mutated into extended-spectrum AmpC (ESAC) variants. Drugs targeting class C β-lactamases, such as nanomolar boronic acid inhibitors (e.g., derivatives mimicking the β-lactam carboxylate), bind covalently to the active-site serine via a tetrahedral boronate intermediate, restoring antibiotic efficacy without typically inducing enzyme overexpression. A standardized numbering scheme (SANC) aids in comparing sequences and structures across diverse bacterial producers. Overall, class C β-lactamases represent a critical enzymatic target in combating multidrug-resistant bacterial infections.

Other names

cephalosporinaseserine β-lactamase class C

Non-β-lactam inhibition via boronic acid forming tetrahedral intermediate with catalytic serine; potentiation of cephalosporins by blocking hydrolysis