Cyanogen as a selective probe for carbonic anhydrase hydrolase activity.
The salt bridge probe cyanogen (ethanedinitrile, C2N2; N identical to C-C identical to N) inhibits the bovine carbonic anhydrase (EC 4.2.1.1.) hydrolase activity toward various types of esters without significant effect on its hydrolyase activity. Two sets of pyridine derivatives that were isosteric substrates for the two activities were differentially affected. Acetazolamide and salamide are reversible inhibitors of the enzyme; only salamide affords protection of the hydrolase activity against the action of C2N2. Since each is known to bind in different positions within the active site, the selective effect of salamide may arise from its position covering one CO2 site as well as a site important for hydrolase activity. The C2N2 concentration dependence of the time course of hydrolase inhibition is consistent with the existence of a high C2N2 affinity site with slow covalent change and a second site with lower C2N2 affinity, but higher rate of covalent modification of the enzyme.
Karagözler
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Department of Chemistry, University of Cincinnati, Ohio 45221-0172.
Ghenbot
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Day
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D000818:Animals; D001665:Binding Sites; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002417:Cattle; D066298:In Vitro Techniques; D015335:Molecular Probes; D009570:Nitriles / Q000494:pharmacology; D013379:Substrate Specificity
D002257:Carbonic Anhydrase Inhibitors; D015335:Molecular Probes; D009570:Nitriles; C011206:cyanogen; D002256:Carbonic Anhydrases