title: Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I-XV.
abstract: We investigated the inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms I-XV with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfamide and other simple or sugar sulfamides, a class of less investigated CA inhibitors (CAIs). The crystal structure of the adduct of hCA II with the boron-substituted sulfamide shows the organic scaffold of this compound bound in the hydrophilic half of the active site where it makes a large number of van der Waals contacts with Ile91, Gln92, Val121, Phe131, Leu198, and Thr200. The data here reported provide further insights into sulfamide binding mechanism confirming that this zinc-binding group could be usefully exploited for obtaining new potent and selective CAIs.
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Fiore
authors.forename: Simona Maria
authors.initials: SM
authors.lastname: Monti
authors.forename: Alessio
authors.initials: A
authors.lastname: Innocenti
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Simone
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000577:Amides / Q000737:chemistry*; D001895:Boron / Q000737:chemistry*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D011485:Protein Binding; D020033:Protein Isoforms; D012996:Solutions; D013451:Sulfonic Acids / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D000577:Amides; D002257:Carbonic Anhydrase Inhibitors; D006841:Hydrocarbons, Aromatic; D020033:Protein Isoforms; D012996:Solutions; D013451:Sulfonic Acids; C005741:sulfamic acid; D002256:Carbonic Anhydrases; D015032:Zinc; D001895:Boron