4HWO

Crystal structure of E. coli Threonyl-tRNA synthetase bound to a novel inhibitor

Summary for 4HWO

• Entry DOI: 10.2210/pdb4hwo/pdb
• Related: 4HWP 4HWR 4HWS 4HWT
• Descriptor: Threonine--tRNA ligase, ZINC ION, N-{[3-(4-aminoquinazolin-7-yl)phenyl]sulfonyl}-L-threoninamide, ... (4 entities in total)
• Functional Keywords: aminoacyl-trna synthetase, protein-inhibitor complex, antibacterial, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• Biological source: Escherichia coli
• Cellular location: Cytoplasm: P0A8M3
• Total number of polymer chains: 2
• Total formula weight: 96930.89

Authors

Hilgers, M.T. (deposition date: 2012-11-08, release date: 2013-09-18, Last modification date: 2024-02-28)

Primary citation

Teng, M.,Hilgers, M.T.,Cunningham, M.L.,Borchardt, A.,Locke, J.B.,Abraham, S.,Haley, G.,Kwan, B.P.,Hall, C.,Hough, G.W.,Shaw, K.J.,Finn, J.
Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design.
J.Med.Chem., 56:1748-1760, 2013

PubMed Abstract: A series of potent and bacteria-selective threonyl-tRNA synthetase (ThrRS) inhibitors have been identified using structure-based drug design. These compounds occupied the substrate binding site of ThrRS and showed excellent binding affinities for all of the bacterial orthologues tested. Some of the compounds displayed greatly improved bacterial selectivity. Key residues responsible for potency and bacteria/human ThrRS selectivity have been identified. Antimicrobial activity has been achieved against wild-type Haemophilus influenzae and efflux-deficient mutants of Escherichia coli and Burkholderia thailandensis.

PubMed: 23362938
DOI: 10.1021/jm301756m

Experimental method

X-RAY DIFFRACTION (1.907 Å)