Serine β-lactamase (SBL)

Serine β-lactamases (SBLs) hydrolyze β-lactam antibiotics and thereby protect bacteria from penicillins, cephalosporins, and related agents^[1]. Mechanistically, class A, C, and D β-lactamases use an active-site serine residue to catalyze β-lactam-ring hydrolysis through an acyl-enzyme intermediate^[2][3]. This catalytic process makes β-lactamase production a major mechanism of acquired β-lactam resistance in Gram-negative pathogens, including Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii^[2]. In disease-relevant models, β-lactamase-mediated resistance affects clinical pathogens and can be evaluated through catalytic activity and inhibition assays^[4]. Compared with metallo-β-lactamases, SBLs are distinct because they use serine-dependent catalysis, whereas class B enzymes require zinc or another metal cofactor^[2][5]. Within SBLs, class A enzymes include clinically important variants, while class C AmpC β-lactamase supports inhibitor design through enzymology, microbiology, and X-ray crystallography^[6]. For experimental applications, clavulanate inhibits selected β-lactamases by forming a stable complex with the active-site serine^[7]. Newer boronic acid inhibitors, including QPX7728, inhibit key serine β-lactamases and support combination studies with multiple β-lactam antibiotics^[8].

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