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'''Crystal structure of S. aureus TyrRS in complex with SB-243545''' | '''Crystal structure of S. aureus TyrRS in complex with SB-243545''' | ||
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[[Category: Qiu, X.]] | [[Category: Qiu, X.]] | ||
[[Category: Smith, W W.]] | [[Category: Smith, W W.]] | ||
[[Category: | [[Category: Staphylococcus aureus]] | ||
[[Category: | [[Category: Structure based inhibitor design]] | ||
[[Category: | [[Category: Truncation]] | ||
[[Category: | [[Category: Tyrosyl-trna synthetase]] | ||
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Revision as of 21:16, 2 May 2008
Crystal structure of S. aureus TyrRS in complex with SB-243545
OverviewOverview
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.
About this StructureAbout this Structure
1JIK is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors., Qiu X, Janson CA, Smith WW, Green SM, McDevitt P, Johanson K, Carter P, Hibbs M, Lewis C, Chalker A, Fosberry A, Lalonde J, Berge J, Brown P, Houge-Frydrych CS, Jarvest RL, Protein Sci. 2001 Oct;10(10):2008-16. PMID:11567092 Page seeded by OCA on Fri May 2 21:16:02 2008