The active site of L-asparaginase: dimethylsulfoxide effect of 5-diazo-4-oxo-L-norvaline interactions.
The asparagine analog, 5-diazo-4-oxo-L-norvaline is a substrate and an irreversible inhibitor of L-asparaginase. Covalent attachment occurs at an increased rate at concentrations of dimethylsulfoxide which reduce the catalytic decomposition of diazo-oxo-norvaline. In 55% dimethylsulfoxide asparaginase is inactivated by diazo-oxo-norvaline (0.05 M) with a t 1/2 of twelve seconds. In aqueous buffer the rate of diazo-oxo-norvaline decomposition is increased three-fold in the presence of the nucleophile hydroxylamine; this nucleophile also protects the enzyme against inactivation by diazo-oxo-norvaline in the presence of dimethylsulfoxide.
Lachman
L B
LB
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Handschumacher
R E
RE
D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D001215:Asparaginase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D001216:Asparagine / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology; D005973:Glutamine / Q000378:metabolism; D006868:Hydrolysis / Q000187:drug effects; D007700:Kinetics
D005973:Glutamine; C002199:5-diazo-4-oxonorvaline; D001216:Asparagine; D000622:Aminolevulinic Acid; D001215:Asparaginase; D004121:Dimethyl Sulfoxide