title: Carbonic anhydrase inhibitors: the X-ray crystal structure of ethoxzolamide complexed to human isoform II reveals the importance of thr200 and gln92 for obtaining tight-binding inhibitors.
abstract: Ethoxzolamide, an almost forgotten inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), is the only classical inhibitor whose structure in adduct with any isoform was not reported yet. We report here the inhibition data of this molecule with the 12 catalytically active mammalian isozymes (CA I-CA XIV) and the X-ray crystal structure with the cytosolic, ubiquitous isoform CA II. These data are presumably useful for the design of novel CA inhibitors, targeting various CA isozymes, considering that ethoxzolamide was already the lead molecule to obtain the second generation inhibitors, dorzolamide and brinzolamide, clinically used antiglaucoma agents with topical action, as well as various other investigational agents.
authors: Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors: Anna
authors: A
authors: Di Fiore
authors: Carlo
authors: C
authors: Pedone
authors: Jochen
authors: J
authors: Antel
authors: Harald
authors: H
authors: Waldeck
authors: Andreas
authors: A
authors: Witte
authors: Michael
authors: M
authors: Wurl
authors: Andrea
authors: A
authors: Scozzafava
authors: Claudiu T
authors: CT
authors: Supuran
authors: Giuseppina
authors: G
authors: De Simone
mesh_terms: D000818:Animals; D001665:Binding Sites; D024402:Carbonic Anhydrase II / Q000737:chemistry* / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis; D018360:Crystallography, X-Ray; D005016:Ethoxzolamide / Q000737:chemistry* / Q000494:pharmacology; D005973:Glutamine / Q000737:chemistry; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013912:Threonine / Q000737:chemistry
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D005973:Glutamine; D013912:Threonine; D024402:Carbonic Anhydrase II; D005016:Ethoxzolamide