Structural Mapping of Anion Inhibitors to β-Carbonic Anhydrase psCA3 from Pseudomonas aeruginosa
| Autor: | Melissa Pinard, Claudiu T. Supuran, Marianna A. Patrauchan, Robert McKenna, A.B. Murray, Daniela Vullo, Mayank Aggarwal |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Bicarbonate 02 engineering and technology medicine.disease_cause Crystallography X-Ray Biochemistry Carbonic Anhydrase II 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Carbonic anhydrase Catalytic Domain Drug Discovery medicine Humans General Pharmacology Toxicology and Pharmaceutics Carbonic Anhydrase Inhibitors Sulfamide Pharmacology chemistry.chemical_classification Sulfonamides biology Thiocyanate Pseudomonas aeruginosa Organic Chemistry Imidazoles 021001 nanoscience & nanotechnology Antimicrobial biology.organism_classification Carbonic Anhydrase III Anti-Bacterial Agents Kinetics 030104 developmental biology Enzyme chemistry biology.protein Molecular Medicine 0210 nano-technology Thiocyanates Pseudomonadaceae Protein Binding |
| Zdroj: | ChemMedChem. 13(19) |
| ISSN: | 1860-7187 |
| Popis: | Pseudomonas aeruginosa is a Gram-negative facultative anaerobe belonging to the Pseudomonadaceae family. It is a multidrug-resistant opportunistic human pathogen, a common cause of life-threatening nosocomial infections, and a key bacterial agent in cystic fibrosis and endocarditis. The bacterium exhibits intrinsic resistance to most antibacterial agents, including aminoglycosides and quinolones. Hence, the identification of new drug targets for P. aeruginosa is ongoing. PsCA3 is a β-class carbonic anhydrase (β-CA) that catalyzes the reversible hydration of carbon dioxide to bicarbonate and represents a new class of antimicrobial target. Previously, inhibitor screening studies of psCA3 have shown that a series of small anions including sulfamide (SFN), imidazole (IMD), and 4-methylimidazole (4MI), and thiocyanate (SCN) inhibit the enzyme with efficiencies in the micro- to millimolar range. Herein the X-ray crystal structures of these inhibitors in complex with psCA3 are presented and compared with human CA II. This structural survey into the binding modes of small anions forms the foundation for the development of inhibitors against β-CAs and more selective inhibitors against P. aeruginosa. |
| Databáze: | OpenAIRE |
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