title: Cloning, characterization and sulfonamide inhibition studies of an α-carbonic anhydrase from the living fossil sponge Astrosclera willeyana.
abstract: The α-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 9.0×10(5) s(-1) and k(cat)/K(m) of 1.1×10(8) M(-1) × s(-1)), and is inhibited by various aromatic/heterocyclic sulfonamides and sulfamates with inhibition constants in the range of 2.9 nM-8.85 μM. 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.
authors.affiliation: Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovak Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Ohradanova
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastorekova
authors.forename: Jaromir
authors.initials: J
authors.lastname: Pastorek
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Jackson
authors.forename: Gert
authors.initials: G
authors.lastname: Wörheide
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D003001:Cloning, Molecular; D005580:Fossils; D006801:Humans; D008969:Molecular Sequence Data; D011161:Porifera / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D016415:Sequence Alignment; D013449:Sulfonamides / Q000037:antagonists & inhibitors*; D013451:Sulfonic Acids / Q000037:antagonists & inhibitors*
chemical_list: D013449:Sulfonamides; D013451:Sulfonic Acids; C005741:sulfamic acid; D002256:Carbonic Anhydrases; C572560:astrosclerin-3, Astrosclera willeyana