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PDBsum entry 4hwr

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protein ligands metals Protein-protein interface(s) links
Ligase/ligase inhibitor PDB id
4hwr
Jmol
Contents
Protein chains
403 a.a.
Ligands
1B2 ×2
Metals
_ZN ×2
Waters ×444
PDB id:
4hwr
Name: Ligase/ligase inhibitor
Title: Crystal structure of e. Coli threonyl-tRNA synthetase bound inhibitor
Structure: Threonine--tRNA ligase. Chain: a, b. Fragment: unp residues 242-642. Synonym: threonyl-tRNA synthetase, thrrs. Engineered: yes
Source: Escherichia coli. Organism_taxid: 83333. Strain: k12. Gene: thrs, b1719, jw1709. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Resolution:
1.90Å     R-factor:   0.267     R-free:   0.303
Authors: M.T.Hilgers
Key ref: M.Teng et al. (2013). Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design. J Med Chem, 56, 1748-1760. PubMed id: 23362938 DOI: 10.1021/jm301756m
Date:
08-Nov-12     Release date:   18-Sep-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A8M3  (SYT_ECOLI) -  Threonine--tRNA ligase
Seq:
Struc:
 
Seq:
Struc:
642 a.a.
403 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.6.1.1.3  - Threonine--tRNA ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + L-threonine + tRNA(Thr) = AMP + diphosphate + L-threonyl-tRNA(Thr)
ATP
+ L-threonine
+ tRNA(Thr)
= AMP
+ diphosphate
+ L-threonyl-tRNA(Thr)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     tRNA aminoacylation for protein translation   2 terms 
  Biochemical function     nucleotide binding     4 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm301756m J Med Chem 56:1748-1760 (2013)
PubMed id: 23362938  
 
 
Identification of bacteria-selective threonyl-tRNA synthetase substrate inhibitors by structure-based design.
M.Teng, M.T.Hilgers, M.L.Cunningham, A.Borchardt, J.B.Locke, S.Abraham, G.Haley, B.P.Kwan, C.Hall, G.W.Hough, K.J.Shaw, J.Finn.
 
  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.