title: On the mechanism of action of vancomycin: inhibition of peptidoglycan synthesis in Gaffkya homari.
abstract: Vancomycin inhibits the synthesis of peptidoglycan in membrane preparations from Gaffkya homari with uridine diphosphate-N-acetylmuramyl (UDP-Mur-NAc)-pentapeptide as substrate, but not with either UDP-MurNAc-tetrapeptide or UDP-MurNAc-tripeptide. These results are correlated with the specificity studies described by Perkins and Nieto for complex formation between the antibiotic and the peptide subunit. It is concluded that the formation of a complex between vancomycin and a postulated cell wall acceptor or between vancomycin and the enzymes involved in peptidoglycan synthesis does not contribute to the inhibitory action of this antibiotic. The mechanism of vancomycin action on peptidoglycan synthesis is clearly different from that of moenomycin and bacitracin. In the presence of these antibiotics, peptidoglycan synthesis is inhibited with both UDP-MurNAc-pentapeptide and -tetrapeptide as substrates. In addition, these results provide additional insight into the mechanism of phospho-MurNAc-pentapeptide translocase. For example, enhancement of the transfer of phospho-MurNAc-peptide from UDP-MurNAc-peptide to undecaprenyl-phosphate at low concentrations of vancomycin is observed with UDP-MurNAc-pentapeptide and not with -tetrapeptide. Complexation of vancomycin with undecaprenyl-diphosphate-MurNAc-pentapeptide, resulting in an ineffective intermediate, would increase the rate of transfer by preventing the reassociation of undecaprenyl-diphosphate-MurNAc-pentapeptide with the enzyme.
mesh_terms: D002250:Carbon Radioisotopes; D003864:Depression, Chemical; D008837:Micrococcus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010457:Peptidoglycan / Q000096:biosynthesis*; D013289:Streptococcaceae / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014178:Translocation, Genetic; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D002250:Carbon Radioisotopes; D010457:Peptidoglycan; D014640:Vancomycin