Aminoalkylaziridines as substrates and inhibitors of lysyl oxidase: specific inactivation of the enzyme by N-(5-aminopentyl)aziridine.
The reaction of lysyl oxidase was assessed with members of a series of aminoalkylaziridines in which the primary amino group and the aziridinyl nitrogen were separated by 3-7 methylene carbons. Among these, N-(5-aminopentyl)aziridine proved to be the poorest substrate by far and to inhibit the enzyme activity. Aminoalkylaziridines with chain lengths shorter or longer than five carbons did not inhibit the enzyme. The resulting inhibition was competitive with productive substrates and became irreversible with time, following pseudo first order kinetics with a KI of 0.22 mM. N-(5-aminopentyl)aziridine appears to act as a bifunctional affinity label covalently interacting with the active site of this enzyme.
Nagan
N
N
Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
Callery
P S
PS
Kagan
H M
HM
D000478:Alkylation; D000588:Amines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001388:Aziridines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology; D013379:Substrate Specificity
D000588:Amines; D001388:Aziridines; D004791:Enzyme Inhibitors; C500553:N-(5-aminopentyl)aziridine; D008249:Protein-Lysine 6-Oxidase