A surface plasmon resonance analysis of the interaction between the antibiotic moenomycin A and penicillin-binding protein 1b.
The antibiotic moenomycin A inhibits the biosynthesis of peptidoglycan, the main structural polymer of the bacterial cell wall. The inhibition is based on a reversible binding of the antibiotic to one of the substrate binding sites in enzymes such as penicillin-binding protein (PBP) 1b. A novel assay based on surface plasmon resonance (SPR) has been established that can be used to investigate selective binding of the moenomycin sugar moiety and other transglycosylase inhibitors to this enzyme. Suitable ligands were prepared from moenomycin A and coupled to SPR sensor surfaces. Moenomycin analogues with structural variations were used to perform competitive SPR experiments with PBP 1b. The SPR results confirm for the first time that the trisaccharide fragment of moenomycin A (C-E-F-G-H-I) is the minimal structure that possesses all moieties sufficient for biological activity and for affinity towards PBP 1b. The method seems to be appropriate for use in screens for transglycosylase inhibitors that bind to the moenomycin-binding site of the enzyme.
D001426:Bacterial Proteins; D001455:Bambermycins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins; D004926:Escherichia coli / Q000187:drug effects; D016695:Glycosyltransferases / Q000037:antagonists & inhibitors; D006602:Hexosyltransferases / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D009097:Multienzyme Complexes / Q000378:metabolism*; D002267:Muramoylpentapeptide Carboxypeptidase; D009844:Oligosaccharides / Q000737:chemistry; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan / Q000096:biosynthesis; D010458:Peptidyl Transferases / Q000378:metabolism*; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000187:drug effects; D020349:Surface Plasmon Resonance
D001426:Bacterial Proteins; D002352:Carrier Proteins; D009097:Multienzyme Complexes; D009844:Oligosaccharides; D046915:Penicillin-Binding Proteins; D010457:Peptidoglycan; D001455:Bambermycins; C437243:moenomycin A; D010458:Peptidyl Transferases; D016695:Glycosyltransferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase