2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid. A potent irreversible inhibitor of diaminopimelic acid epimerase. Spontaneous formation from alpha-(halomethyl)diaminopimelic acids.
2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid (3) (aziridino-DAP) was identified as the product of spontaneous hydrolysis of alpha-(halomethyl)diaminopimelic acids (alpha-halomethyl-DAPs) 2a-c. Under physiological conditions, 3 is an extremely potent irreversible inhibitor of the bacterial enzyme diaminopimelic acid epimerase (DAP-epimerase; EC 5.1.1.7). This unusual mode of action of an alpha-halomethyl amino acid with a non-pyridoxal enzyme is investigated. Synthesis and characterization of 2a-c and 3, kinetics of spontaneous formation of 3 from alpha-halomethyl-DAPs, and kinetics of enzyme inhibition by both 3 and by alpha-halomethyl-DAPs are reported.
Gerhart
F
F
Merrell Dow Research Institute, Strasbourg Center, France.
Higgins
W
W
Tardif
C
C
Ducep
J B
JB
D000591:Amino Acid Isomerases; D000599:Amino Acids, Diamino; D001388:Aziridines / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives; D004926:Escherichia coli / Q000201:enzymology; D006868:Hydrolysis; D007535:Isomerases / Q000037:antagonists & inhibitors*; D007700:Kinetics; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors*; D013816:Thermodynamics
D000599:Amino Acids, Diamino; D001388:Aziridines; C065055:2-(4-amino-4-carboxybutyl)-2-aziridinecarboxylic acid; D003960:Diaminopimelic Acid; D007535:Isomerases; D019998:Racemases and Epimerases; D000591:Amino Acid Isomerases; C042032:diaminopimelate epimerase