Cyanogen-induced gamma-glutamyl to imidazole cross-link in carbonic anhydrase. A unique mode of inhibition.
The irreversible inhibition of carbonic anhydrase by cyanogen occurs by a unique mechanism. Cyanogen is an affinity label: it behaves like a carbodiimide and produces an intra-molecular cross-link without being incorporated. The nucleophile-labile cross-link is formed between a gamma-COOH of a Glu and an imidazole of a His with a 1:1:1 stoichiometry with the enzyme. The deletion of approximately 1 Glu and approximately 1 His was noted by amino acid analysis of enzymatically hydrolyzed carbonic anhydrase. The modified Glu was converted to 2,4-diaminobutanoic acid and quantitated by amino acid analysis. The presence and quantity of modified His was supported through high-resolution proton NMR analysis.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D003432:Cross-Linking Reagents; D005973:Glutamine / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009570:Nitriles / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D000596:Amino Acids; D002257:Carbonic Anhydrase Inhibitors; D003432:Cross-Linking Reagents; D007093:Imidazoles; D009570:Nitriles; D005973:Glutamine; C011206:cyanogen; D002256:Carbonic Anhydrases