Molecular basis for the origin of differential spectral and binding profiles of dansylamide with human carbonic anhydrase I and II
| Autor: | D. K. Srivastava, Abir L. Banerjee, Sanku Mallik, Bratati Ganguly, Shakila Tobwala |
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| Rok vydání: | 2005 |
| Předmět: |
Carbonic Anhydrase I
Stereochemistry Macromolecular Substances Ligands Biochemistry Carbonic Anhydrase II law.invention Structure-Activity Relationship law Humans Fluorescent Dyes chemistry.chemical_classification Dansyl Compounds Binding Sites Spectral properties Hydrogen-Ion Concentration Sulfonamide Kinetics Spectrometry Fluorescence chemistry Models Chemical Recombinant DNA Thermodynamics Protein Binding |
| Zdroj: | Biochemistry. 44(10) |
| ISSN: | 0006-2960 |
| Popis: | Sulfonamide derivatives serve as potent inhibitors of carbonic anhydrases (CAs), and a few such inhibitors have been currently used as drugs for the treatment of different pathogenic conditions in humans. In pursuit of designing the isozyme-specific inhibitors of human CAs, we observed that the fluorescence spectral properties and binding profiles of a fluorogenic sulfonamide derivative, 5-(dimethylamino)-1-naphthalenesulfonamide (dansylamide, DNSA), were markedly different between the recombinant forms of human carbonic anhydrase I (hCA I) and II (hCA II). The kinetic evaluation of the overall microscopic pathways for the binding of DNSA to hCA I versus hCA II revealed that the protein isomerization step served as a major determinant of the above discrepancy. Arguments are presented that the detailed structural−functional investigations of enzyme−ligand interactions may provide insights into designing the isozyme-specific inhibitors of CAs. |
| Databáze: | OpenAIRE |
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