1JIK

Crystal structure of S. aureus TyrRS in complex with SB-243545

Summary for 1JIK

• Entry DOI: 10.2210/pdb1jik/pdb
• Related: 1JII 1JIJ 1JIL
• Descriptor: tyrosyl-tRNA synthetase, [2-AMINO-3-(4-HYDROXY-PHENYL)-PROPIONYLAMINO]-(1,3,4,5-TETRAHYDROXY-4-HYDROXYMETHYL-PIPERIDIN-2-YL)- ACETIC ACID BUTYL ESTER (3 entities in total)
• Functional Keywords: tyrosyl-trna synthetase, staphylococcus aureus, truncation, structure based inhibitor design, ligase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 48126.95

Authors

Qiu, X.,Janson, C.A.,Smith, W.W.,Jarvest, R.L. (deposition date: 2001-07-02, release date: 2001-10-26, Last modification date: 2024-02-07)

Primary citation

Qiu, X.,Janson, C.A.,Smith, W.W.,Green, S.M.,McDevitt, P.,Johanson, K.,Carter, P.,Hibbs, M.,Lewis, C.,Chalker, A.,Fosberry, A.,Lalonde, J.,Berge, J.,Brown, P.,Houge-Frydrych, C.S.,Jarvest, R.L.
Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors.
Protein Sci., 10:2008-2016, 2001

PubMed Abstract: 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.

PubMed: 11567092
DOI: 10.1110/ps.18001

Experimental method

X-RAY DIFFRACTION (2.8 Å)