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

Abstract

Glutamate semialdehyde aminomutase is a recognized target for selective herbicides and antibacterial agents because it provides the aminolevulinate from which tetrapyrroles are synthesized in plants and bacteria but not in animals. The reactions of the enzyme with R- and S-enantiomers of a novel compound, diaminopropyl sulfate, designed as a mechanism-based inhibitor of the enzyme are described. The S-enantiomer undergoes transamination without significantly inactivating the enzyme. The R-enantiomer inactivates the enzyme rapidly. Inactivation is accompanied by the formation of a 520 nm-absorbing chromophore and by the elimination of sulfate. The inactivation is attenuated by simultaneous transamination of the enzyme to its pyridoxamine phosphate form but inclusion of succinic semialdehyde to reverse the transamination leads to complete inactivation. The inactivation is attributed to further reactions arising from generation of an external aldimine between the pyridoxal phosphate cofactor and the 2,3-diaminopropene that results from enzyme-catalyzed beta-elimination of sulfate.