X-ray crystallographic and kinetic investigations of 6-sulfamoyl-saccharin as a carbonic anhydrase inhibitor
Autor: | A. Di Fiore, Simona Maria Monti, V. Alterio, Jekaterina Ivanova, Raivis Zalubovskis, G. De Simone, Caudiu Trandafir Supuran, Muhammet Tanc, I. V. Vozny |
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Rok vydání: | 2015 |
Předmět: |
Models
Molecular Stereochemistry medicine.drug_class Crystallography X-Ray Biochemistry Adduct chemistry.chemical_compound Deprotonation Saccharin Catalytic Domain medicine Moiety Humans Carbonic anhydrase inhibitor Physical and Theoretical Chemistry Carbonic Anhydrase Inhibitors Carbonic Anhydrases chemistry.chemical_classification Sulfonamides biology Chemistry Organic Chemistry Active site Lyase Sulfonamide Isoenzymes Kinetics biology.protein psychological phenomena and processes |
Zdroj: | Organicbiomolecular chemistry. 13(13) |
ISSN: | 1477-0539 |
Popis: | 6-Sulfamoyl-saccharin was investigated as an inhibitor of 11 α-carbonic anhydrase (CA, EC 4.2.1.1) isoforms of human (h) origin, hCA I-XIV, and X-ray crystallographic data were obtained for its adduct with hCA II, the physiologically dominant isoform. This compound possesses two potential zinc-binding groups, the primary sulfamoyl one and the secondary, acylatedsulfonamide. Saccharin itself binds to the Zn(II) ion from the CA active site coordinating with this last group, in deprotonated (SO2N(-)CO) form. Here we explain why 6-sulfamoyl-saccharin, unlike saccharin, binds to the metal ion from the hCA II active site by its primary sulfonamide moiety and not the secondary one as saccharin itself. Our study is useful for shedding new light to the structure-based drug design of isoform-selective CA inhibitors of the sulfonamide type. |
Databáze: | OpenAIRE |
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