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ID: ALA1146311

Journal: Bioorg Med Chem Lett

Title: Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV.

Authors: Temperini C, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT.

Abstract: The activation of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with L-adrenaline and histamine has been investigated by kinetic and X-ray crystallographic studies. L-Adrenaline behaves as a potent activator of isozyme CA I (activation constant of 90 nM), being a much weaker activator of isozyme CA II (activation constant of 96 microM). Isoforms CA IV, VA, VII, and XIV were activated by L-adrenaline with K(A)s in the range of 36-63 microM. The X-ray crystal structure of the CA II-L-adrenaline adduct revealed that the activator plugs the entrance of the active site cavity, obstructing it almost completely.

CiteXplore: 17127057

DOI: 10.1016/j.bmcl.2006.11.027