The Bactericidal action of β-lactam antibiotics is related to covalent modification of transpeptidases, enzymes that take part in the synthesis of bacterial cell wall. The β-lactam moiety mimics the transpeptidase substrate and irreversibly inhibits the enzyme. In penicillin and cephalosporin, the β-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 β-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 β-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).
Duszyński et al. (Tue,) studied this question.