Molecular recognition and binding of CcrA from Bacteroides fragilis with cefotaxime and ceftazidime by fluorescence spectra and molecular docking.

In search of new super-bacterial inhibitor agents, the recognition and binding mechanism of the B1 subclass MβL CcrA from Bacteroides fragilis with cefotaxime (CTX) and ceftazidime (CAZ) were studied using spectroscopy analysis and molecular docking. The results showed that the fluorescence quenching of CcrA induced by CTX and CAZ were all due to the complex formation, which belonged to static quenching and was forced by hydrogen bonds and Van der Waals forces, despite the greater binding ability of CTX with CcrA than CAZ. Upon recognizing CTX or CAZ, the CcrA opened its binding pocket by the microenvironmental and conformational of three loops changing to promote an induced-fit of the freshly introduced antibiotics. In addition, the whole antibiotic molecule ultimately entered the active pocket of CcrA with its original carbonate replaced by the carboxyl oxygen of the hexatomic ring adjacent to the β-lactam ring in CTX or CAZ, forming a new tetrahedral coordination structure at the Zn2 site. Moreover, the difference in steric hindrance and electrostatic effects of the side chain affected the binding ability of the two antibiotics to the CcrA. This work showed the refined procedures of the antibiotics binding to CcrA and might provide useful information hint for the new strategy of developing the novel and innovative super-bacterial antibiotics.