title: Carbonic anhydrase inhibitors: inhibition of human, bacterial, and archaeal isozymes with benzene-1,3-disulfonamides--solution and crystallographic studies.
abstract: Three benzene-1,3-disulfonamide derivatives were investigated for their interaction with 12 mammalian alpha-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to the alpha-, beta-, and gamma-CA class, respectively. X-ray crystal structure of the three inhibitors in complex with the dominant human isozyme CA II revealed a particular binding mode within the cavity. The sulfonamide group in meta-position to the Zn(2+)-coordinated SO(2)NH(2) moiety was oriented toward the hydrophilic side of the active site cleft, establishing hydrogen bonds with His64, Asn67, Gln92, and Thr200. The plane of the phenyl moiety of the inhibitors was rotated by 45 degrees and tilted by 10 degrees with respect to its most recurrent orientation in other CA II-sulfonamide complexes.
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Alterio
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Simone
authors.forename: Simona Maria
authors.initials: SM
authors.lastname: Monti
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000187:drug effects*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D002256:Carbonic Anhydrases