Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors
| Autor: | Kyung O. Johanson, Ward W. Smith, Andrew P. Fosberry, Judith LaLonde, Patrick McDevitt, Pamela Brown, Xiayang Qiu, Susan M. Green, Martin Hibbs, Richard L. Jarvest, Catherine S. V. Houge-Frydrych, Cheryl A. Janson, Ceri J. Lewis, Alison F Chalker, Paul S. Carter, John M. Berge |
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| Jazyk: | angličtina |
| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Staphylococcus aureus Stereochemistry Protein Conformation Mutant Molecular Sequence Data Biology medicine.disease_cause Crystallography X-Ray Biochemistry Article Piperidines Tyrosine-tRNA Ligase medicine Amino Acid Sequence Binding site Enzyme Inhibitors Furans Molecular Biology chemistry.chemical_classification DNA ligase Sequence Homology Amino Acid Substrate (chemistry) Dipeptides Antimicrobial Bridged Bicyclo Compounds Heterocyclic Enzyme Tyrosine—tRNA ligase chemistry Crystallization |
| Popis: | SB-219383 and its analogues are a class of potent and specific inhibitors of bacterial tyrosyl-tRNA synthetases. Crystal structures of these inhibitors have been solved in complex with the tyrosyl-tRNA synthetase from Staphylococcus aureus, the bacterium that is largely responsible for hospital-acquired infections. The full-length enzyme yielded crystals that diffracted to 2.8 A resolution, but a truncated version of the enzyme allowed the resolution to be extended to 2.2 A. These inhibitors not only occupy the known substrate binding sites in unique ways, but also reveal a butyl binding pocket. It was reported that the Bacillus stearothermophilus TyrRS T51P mutant has much increased catalytic activity. The S. aureus enzyme happens to have a proline at position 51. Therefore, our structures may contribute to the understanding of the catalytic mechanism and provide the structural basis for designing novel antimicrobial agents. |
| Databáze: | OpenAIRE |
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