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

Molecular Classification

Enzyme, Hydrolase (amide hydrolase; EC 3.5.2.6), β-Lactamase, Class A (Ambler classification; serine-based)

Other Names

Class A β-lactamase, Serine 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-lactamases, KPC carbapenemase (Klebsiella pneumoniae carbapenemase; Class A serine carbapenemase)

Disease Roles

Infection (antimicrobial resistance in Gram-negative and some Gram-positive bacteria)

Class A serine beta-lactamase Overview

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.

Mechanism of Action

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)

Biological Functions

Hydrolysis of β-lactam antibiotics (ring opening)

Antibiotic resistance mechanism in bacteria

Disease Associations

Infection (antimicrobial resistance in Gram-negative and some Gram-positive bacteria)

Safety Considerations

Therapeutic challenge: enzyme-mediated resistance leading to β-lactam treatment failure and limited options in serious Gram-negative infections
Evolution and spread of extended-spectrum and carbapenemase variants (e.g., CTX-M, KPC) complicate inhibitor efficacy and stewardship

Interacting Drugs

β-lactam antibiotics: penicillins, cephalosporins, monobactams; some Class A variants also hydrolyze carbapenems

β-lactamase inhibitors: clavulanic acid, tazobactam, sulbactam (mechanism-based inhibitors of many Class A enzymes)

Newer β-lactamase inhibitor combinations target Class A enzymes: e.g., avibactam (with ceftazidime) inhibits many Class A including KPC; note: specific pairing is an informed extension consistent with Class A inhibitor profiles described by functional classification

Associated Biomarkers

Biomarker
Presence of genes encoding Class A enzymes (e.g., blaTEM, blaCTX-M, blaKPC) in isolates as markers of resistance; detection guides therapy choices