Carbonic anhydrase inhibitors. Inhibition studies of the human secretory isoform VI with anions.
The unique secretory isozyme of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VI, has been cloned, expressed, and purified. The kinetic parameters for the CO(2) hydration reaction proved hCA VI to possess a k(cat) of 3.4x10(5)s(-1) and k(cat)/K(M) of 4.9x10(7)M(-1)s(-1) (at pH 7.5 and 20 degrees C). hCA VI has a significant catalytic activity for the physiological reaction, of the same order of magnitude as isoforms CA I or CA IX. A series of anions (such as bicarbonate, chloride, nitrate, etc.) were shown to inhibit the activity of the enzyme, with inhibition constants typically in the range of 0.60-0.90mM. The best hCA VI inhibitors were cyanide, azide, sulfamide, and sulfamate, with inhibition constants in the range of 70-90microM.
Nishimori
Isao
I
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Innocenti
Alessio
A
Vullo
Daniela
D
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000086:Acetazolamide / Q000494:pharmacology; D000595:Amino Acid Sequence; D000838:Anions / Q000494:pharmacology*; D002021:Buffers; D002245:Carbon Dioxide / Q000737:chemistry; D030741:Carbonic Anhydrase IV / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000737:chemistry; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002384:Catalysis; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008667:Metalloproteins / Q000737:chemistry; D008969:Molecular Sequence Data
D000838:Anions; D002021:Buffers; D002257:Carbonic Anhydrase Inhibitors; D008667:Metalloproteins; D002245:Carbon Dioxide; D030741:Carbonic Anhydrase IV; D000086:Acetazolamide