Serine beta-lactamase (Classes A, C, and D) (SBL)

Serine beta-lactamases (Classes A, C, and D) are bacterial enzymes that catalyze the hydrolysis of the beta-lactam ring, the core structural component of many widely used antibiotics such as penicillins, cephalosporins, and carbapenems (Bush & Jacoby, 2010, PMID: 20008565). These enzymes are classified based on their primary sequence homology under the Ambler classification system, utilizing a conserved serine residue in their active site to initiate a nucleophilic attack on the beta-lactam bond (Ambler, 1980, PMID: 7005956). Class A includes common enzymes like TEM, SHV, and the KPC carbapenemase; Class C includes AmpC cephalosporinases; and Class D includes OXA-type enzymes (Drawz & Bonomo, 2010, PMID: 20065074). Their production by pathogenic bacteria is a primary driver of antimicrobial resistance, rendering standard treatments ineffective and leading to increased morbidity in hospital-acquired infections. Therapeutic strategies involve the use of beta-lactamase inhibitors, such as clavulanic acid or newer agents like avibactam and durlobactam, which bind to and deactivate these enzymes to protect co-administered antibiotics (Papp-Wallace et al., 2011, PMID: 21464369). The ongoing evolution of these enzymes, particularly the emergence of extended-spectrum beta-lactamases (ESBLs) and carbapenemases, remains a significant challenge for global public health and drug development.

Other names

Ambler Class A, C, and D beta-lactamasesSerine-based beta-lactamasesPenicillinaseCephalosporinaseOxacillinaseSerine beta-lactamases

Inhibition of the enzyme's catalytic activity by forming a stable covalent acyl-enzyme intermediate with the active-site serine residue, thereby preventing the hydrolysis of co-administered beta-lactam antibiotics (Drawz & Bonomo, 2010, PMID: 20065074).