Inhibition of glucosamine synthase by bacilysin and anticapsin.
L-Glutamine:D-fructose-6-phosphate amidotransferase ('glucosamine synthase', EC 5.3.1.19) from Escherichia coli MRE 600 was purified at least 75-fold. It catalysed the formation of 21.1 mumol glucosamine 6-phosphate (mg protein)-1 in 30 min at 37 degrees C. Its molecular weight, estimated by gel filtration, was about 90000 and it was inhibited by thiol group reagents. Anticapsin, the C-terminal amino acid of the dipeptide antibiotic bacilysin, and to a lesser extent bacilysin itself, inhibited glucosamine synthase activity. Kinetic studies indicated that the inhibition was non-competitive with respect to fructose 6-phosphate as substrate but partly competitive with respect to L-glutamine. Incubation of the enzyme with anticapsin brought about a time-dependent and irreversible inhibition. It is suggested that anticapsin behaves as a glutamine analogue and that a reaction of its epoxide group with a thiol group of glucosamine synthase results in its linkage to the enzyme by a covalent bond.
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002238:Carbohydrate Epimerases / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics
D000900:Anti-Bacterial Agents; D004151:Dipeptides; C000097:anticapsin; C006674:bacilysin; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D002238:Carbohydrate Epimerases; D000409:Alanine