PDBsum entry 2d1f

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Lyase PDB id
Protein chains
349 a.a. *
PLP ×2
Waters ×54
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Structure of mycobacterium tuberculosis threonine synthase
Structure: Threonine synthase. Chain: a, b. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.191     R-free:   0.256
Authors: A.S.Covarrubias,T.Bergfors,K.Mannerstedt,S.Oscarson,T.A.Jone S.L.Mowbray,M.Hogbom
Key ref:
A.S.Covarrubias et al. (2008). Structural, biochemical, and in vivo investigations of the threonine synthase from Mycobacterium tuberculosis. J Mol Biol, 381, 622-633. PubMed id: 18621388 DOI: 10.1016/j.jmb.2008.05.086
20-Aug-05     Release date:   05-Sep-06    
Go to PROCHECK summary

Protein chains
P9WG59  (THRC_MYCTU) -  Threonine synthase
360 a.a.
349 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Threonine synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Threonine Biosynthesis
      Reaction: O-phospho-L-homoserine + H2O = L-threonine + phosphate
+ H(2)O
= L-threonine
+ phosphate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plasma membrane   2 terms 
  Biological process     growth   4 terms 
  Biochemical function     lyase activity     3 terms  


DOI no: 10.1016/j.jmb.2008.05.086 J Mol Biol 381:622-633 (2008)
PubMed id: 18621388  
Structural, biochemical, and in vivo investigations of the threonine synthase from Mycobacterium tuberculosis.
A.S.Covarrubias, M.Högbom, T.Bergfors, P.Carroll, K.Mannerstedt, S.Oscarson, T.Parish, T.A.Jones, S.L.Mowbray.
Threonine biosynthesis is a general feature of prokaryotes, eukaryotic microorganisms, and higher plants. Since mammals lack the appropriate synthetic machinery, instead obtaining the amino acid through their diet, the pathway is a potential focus for the development of novel antibiotics, antifungal agents, and herbicides. Threonine synthase (TS), a pyridoxal-5-phosphate-dependent enzyme, catalyzes the final step in the pathway, in which L-homoserine phosphate and water are converted into threonine and inorganic phosphate. In the present publication, we report structural and functional studies of Mycobacterium tuberculosis TS, the product of the rv1295 (thrC) gene. The structure gives new insights into the catalytic mechanism of TSs in general, specifically by suggesting the direct involvement of the phosphate moiety of the cofactor, rather than the inorganic phosphate product, in transferring a proton from C4' to C(gamma) in the formation of the alphabeta-unsaturated aldimine. It further provides a basis for understanding why this enzyme has a higher pH optimum than has been reported elsewhere for TSs and gives rise to the prediction that the equivalent enzyme from Thermus thermophilus will exhibit similar behavior. A deletion of the relevant gene generated a strain of M. tuberculosis that requires threonine for growth; such auxotrophic strains are frequently attenuated in vivo, indicating that TS is a potential drug target in this organism.
  Selected figure(s)  
Figure 3.
Fig. 3. Comparison of MtTS and TtTS active sites. Active-site residues of MtTS and the bound PLP are shown in gold, and equivalent residues of TtTS are in gray. Two important hydrogen bonds mentioned in the text are indicated by black dotted lines. Electron density is for the PLP in the last 2|F[o]| − |F[c]| map prior to its inclusion in the model, contoured at 1 σ = 0.2 e/Å^3.
Figure 5.
Fig. 5. Features of particular interest in the TS catalytic mechanism. A stereo view illustrates how the involvement of the PLP 5′-phosphate group in the conversion of β,γ-unsaturated ketimine to α,β-unsaturated aldimine is suggested by the proximity of the relevant groups in the modeled reaction intermediate, based on superposition of the Tt–AP5 structure (shown by dotted lines). Residues that could influence the pH optimum, as discussed in the text, are shown for MtTS (gold carbons) and EcTS (cyan carbons).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 381, 622-633) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19761441 D.E.Graham, S.M.Taylor, R.Z.Wolf, and S.C.Namboori (2009).
Convergent evolution of coenzyme M biosynthesis in the Methanosarcinales: cysteate synthase evolved from an ancestral threonine synthase.
  Biochem J, 424, 467-478.  
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