Differential inhibition of homotrimeric dUTPases by the 3'-azido derivative of dideoxy-UTP
| Autor: | Jan-Olov Kvassman, Lorena Gonzalez Palmén |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Pharmacology
chemistry.chemical_classification biology Active site Substrate (chemistry) Uridine Triphosphate General Medicine biology.organism_classification Differential inhibition Virus Equine infectious anemia chemistry.chemical_compound Enzyme chemistry Biochemistry Catalytic Domain Drug Discovery biology.protein Enzyme Inhibitors Pyrophosphatases Pathogen Derivative (chemistry) |
| Zdroj: | Journal of enzyme inhibition and medicinal chemistry. 25(1) |
| ISSN: | 1475-6374 |
| Popis: | The inhibitory effects of 3'-azido-2',3'-dideoxyuridine-5'-triphosphate in complex with the Mg2+ ion (azido-ddUTP.Mg) on the dUTPases of the human, E. coli, and equine infectious anemia virus have been compared. Azido-ddUTP is analogous to drugs used in the treatment of HIV. Here it is shown to inhibit the bacterial dUTPase in a competitive manner (Ki = 9.3 microM), but to exhibit only marginal or no binding to the human and viral dUTPases, respectively. This is the first demonstration of an inhibitor with a strong preference for binding to a bacterial dUTPase over the human enzyme. The specific binding to the E. coli dUTPase is surprising in view of the close to identical substrate pockets among the three dUTPases tested. The results are discussed with reference to the possibility of designing active site directed inhibitors that bind to the homotrimeric dUTPase of a pathogen but not to the human form. |
| Databáze: | OpenAIRE |
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