Reactions of glutamate 1-semialdehyde aminomutase with R- and S-enantiomers of a novel, mechanism-based inhibitor, 2,3-diaminopropyl sulfate

Glutamate semialdehyde aminomutase is a recognized target for selective her bicides and antibacterial agents because it provides the aminolevulinate fr om which tetrapyrroles are synthesized in plants and bacteria but not in an imals. The reactions of the enzyme with R- and S-enantiomers of a novel com pound, diaminopropyl sulfate, designed as a mechanism-based inhibitor of th e enzyme are described. The S-enantiomer undergoes transamination without s ignificantly inactivating the enzyme. The R-enantiomer inactivates the enzy me rapidly. Inactivation is accompanied by the formation of a 520 nm-absorb ing chromophore and by the elimination of sulfate. The inactivation is atte nuated by simultaneous transamination of the enzyme to its pyridoxamine pho sphate form but inclusion of succinic semialdehyde to reverse the transamin ation leads to complete inactivation. The inactivation is attributed to fur ther reactions arising from generation of an external aldimine between the pyridoxal phosphate cofactor and the 2,3 diaminopropene that results from e nzyme-catalyzed beta-elimination of sulfate.