Cloning, characterization and sulfonamide inhibition studies of an alpha-carbonic anhydrase from the living fossil sponge Astrosclera willeyana.
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Ohradanova A, Vullo D, Pastorekova S, Pastorek J, Jackson DJ, Worheide G, Supuran CT
Cloning, characterization and sulfonamide inhibition studies of an alpha-carbonic anhydrase from the living fossil sponge Astrosclera willeyana.
Bioorg Med Chem. 2012 Feb 15;20(4):1403-10. doi: 10.1016/j.bmc.2012.01.007. Epub 2012 Jan 12.
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- Abstract
The alpha-carbonic anhydrase (CA, EC 4.2.1.1) Astrosclerin-3 previously isolated from the living fossil sponge Astrosclera willeyana (Jackson et al., Science 2007, 316, 1893), was cloned, kinetically characterized and investigated for its inhibition properties with sulfonamides and sulfamates. Astrosclerin-3 has a high catalytic activity for the CO(2) hydration reaction to bicarbonate and protons (k(cat) of 9.0x10(5) s(-1) and k(cat)/K(m) of 1.1x10(8) M(-1) x s(-1)), and is inhibited by various aromatic/heterocyclic sulfonamides and sulfamates with inhibition constants in the range of 2.9 nM-8.85 muM. Astrosclerin, and the human isoform CA II, display similar kinetic properties and affinities for sulfonamide inhibitors, despite more than 550 million years of independent evolution. Because Astrosclerin-3 is involved in biocalcification, the inhibitors characterized here may be used to gain insights into such processes in other metazoans.
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