title: Crystal structure of the complex between human carbonic anhydrase II and the aromatic inhibitor 1,2,4-triazole.
abstract: The X-ray crystal structure of the complex between human carbonic anhydrase II and the inhibitor 1,2,4-triazole has been refined at 1.9 A resolution to a final R-factor of 0.153. Triazole is an analogue of the competitive inhibitor imidazole, but the crystal structure shows a different type of binding to the enzyme. 1,2,4-Triazole is directly bound to the zinc(II) ion through the nitrogen in position 4, replacing the native water/hydroxyl (Wat263) in a distorted four-co-ordinated complex. The interaction of the inhibitor with the active site is completed by two hydrogen bonds to O gamma of Thr200 and to the amide nitrogen atom of Thr199 through the two adjacent N-1 and N-2 atoms. The binding site of triazole overlaps the proposed binding sites for the substrates, explaining the observed competitive behaviour of the inhibitor towards CO2/HCO3- under equilibrium conditions.
authors.affiliation: Department of Chemistry, University of Siena, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mangani
authors.forename: A
authors.initials: A
authors.lastname: Liljas
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000648:ultrastructure*; D003461:Crystallography; D005583:Fourier Analysis; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D015394:Molecular Structure; D014230:Triazoles / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D014230:Triazoles; D014867:Water; C045575:1,2,4-triazole; D002256:Carbonic Anhydrases; D015032:Zinc