Presence of a histidine at the active site of the neutral endopeptidase-24.11.
Diethylpyrocarbonate treatment of the neutral endopeptidase (EC 3.4.24.11) inhibits both catalytic activity and binding of the inhibitor [3H]-N(R,S)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]-glycine. The loss of activity can be reversed by hydroxylamine and almost completely prevented by the competitive inhibitor phenylalanyl-leucine suggesting the presence, as in thermolysin, of a histidine residue at the active site. Butanedione treatment also reduces both catalytic activity and [3H] inhibitor binding. Phenylalanyl-leucine completely protects from the butanedione induced loss of activity, providing further evidence for an essential arginine at the active site. In contrast, the tyrosine modifying agent N-acetylimidazole has no apparent effect on enzyme activity.
D000818:Animals; D001665:Binding Sites; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D010450:Endopeptidases / Q000032:analysis*; D004852:Epoxy Compounds / Q000494:pharmacology; D006639:Histidine / Q000032:analysis*; D007093:Imidazoles / Q000494:pharmacology; D015260:Neprilysin; D011817:Rabbits; D013820:Thermolysin / Q000378:metabolism; D013997:Time Factors
D004852:Epoxy Compounds; D007093:Imidazoles; D006639:Histidine; C007366:diepoxybutane; D010450:Endopeptidases; D015260:Neprilysin; D013820:Thermolysin; D004047:Diethyl Pyrocarbonate; C012160:N-acetylimidazole