Ambler class D serine beta-lactamase (OXA) (OXA)

Ambler class D serine beta-lactamases, primarily known as OXA-type enzymes (oxacillinases), are a diverse group of bacterial enzymes that catalyze the hydrolysis of the beta-lactam ring, thereby inactivating a wide range of antibiotics including penicillins, cephalosporins, and carbapenems [Poirel et al., 2010, https://pmc.ncbi.nlm.nih.gov/articles/PMC2897466/]. These enzymes are characterized by a unique active-site serine residue that is often carbamylated by CO2 to facilitate catalysis, a structural feature that distinguishes them from Class A and C serine beta-lactamases [Golemi et al., 2001, https://pubmed.ncbi.nlm.nih.gov/11459464/]. Class D enzymes are particularly significant in the context of global antimicrobial resistance, as they are frequently found in Gram-negative pathogens such as Acinetobacter baumannii and Klebsiella pneumoniae, where they contribute to carbapenem-resistant phenotypes [Antunes et al., 2014, https://pubmed.ncbi.nlm.nih.gov/24263465/]. Because many Class D enzymes are poorly inhibited by traditional inhibitors like clavulanic acid or tazobactam, they represent a significant therapeutic challenge in treating multi-drug resistant infections. Modern drug development has focused on novel diazabicyclooctane (DBO) and boronate-based inhibitors, such as avibactam and durlobactam, which are designed to covalently bind the active site and restore the efficacy of partner antibiotics like ceftazidime or sulbactam [Papp-Wallace et al., 2023, https://pubmed.ncbi.nlm.nih.gov/37196645/]. The "selected" clinically relevant variants, such as OXA-48 and OXA-23, are major targets for these new therapeutic combinations. Resistance to these inhibitors is already emerging through specific mutations in the enzyme's active site, necessitating ongoing research into next-generation inhibitors [Leonard et al., 2013, https://pubmed.ncbi.nlm.nih.gov/23939898/].

Other names

OXA-type beta-lactamaseClass D beta-lactamaseOxacillinaseCarbapenem-hydrolyzing class D beta-lactamaseCHDLSelected Ambler class D serine beta-lactamases

Inhibition of the enzyme's catalytic activity through the formation of a stable, slowly reversible or irreversible covalent acyl-enzyme complex with the active-site serine residue, thereby preventing the hydrolysis of beta-lactam antibiotics [Papp-Wallace et al., 2023, https://pubmed.ncbi.nlm.nih.gov/37196645/].