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Complex of Ovine Serum Albumin with Hydrolyzed Ampicillin
Structural highlights
Publication Abstract from PubMedThe Bactericidal action of beta-lactam antibiotics is related to covalent modification of transpeptidases, enzymes that take part in the synthesis of bacterial cell wall. The beta-lactam moiety mimics the transpeptidase substrate and irreversibly inhibits the enzyme. In penicillin and cephalosporin, the beta-lactam ring is coupled with a five-membered thiazolidine ring or a six-membered dihydrothiazine ring, respectively. In the case of penicillins, such conjunction causes higher tension of this bicyclic moiety; therefore, the beta-lactam ring can be hydrolyzed in certain conditions, inactivating the antibiotic. Serum albumin is known for its drug binding capabilities, which enable it to transport pharmaceuticals through the circulatory system. Penicillins and cephalosporins are no exception in this aspect, and they are also carried by serum albumin in the bloodstream. In this study, we structurally investigate the ability of three serum albumins-equine (ESA), caprine (CSA), and ovine (OSA)-to bind two penicillins, ampicillin (Amp) and oxacillin (Oxa), and two cephalosporins, cefaclor (Cef) and cephalosporin C (Csc). The crystal structures of these mammalian serum albumin complexes shed new light on the albumin binding properties of beta-lactam antibiotics, showing one common binding site for Amp, Oxa, and Cef in Fatty Acid Site 6 (FA6), and a second cefaclor molecule bound in domain I of the equine serum albumin. It was surprising that these antibiotics are not bound in the main drug binding site. However, cephalosporin C is bound in OSA Drug Site 1 (DS1). Structural Interactions of beta-Lactam Antibiotics with Mammalian Serum Albumins.,Duszynski K, Sekula B, Talaj J, Bujacz A Int J Mol Sci. 2026 Jan 13;27(2):776. doi: 10.3390/ijms27020776. PMID:41596427[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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