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PDBsum entry 2c2b

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protein ligands Protein-protein interface(s) links
Synthase PDB id
2c2b
Jmol
Contents
Protein chains
(+ 0 more) 445 a.a. *
Ligands
SAM ×12
TRS ×3
Waters ×313
* Residue conservation analysis
PDB id:
2c2b
Name: Synthase
Title: Crystallographic structure of arabidopsis thaliana threonine synthase complexed with pyridoxal phosphate and s-adenosylmethionine
Structure: Threonine synthase 1, chloroplastic. Chain: a, b, c, d, e, f. Synonym: threonine synthase, ts, protein methionine over-accumulator 2. Engineered: yes
Source: Arabidopsis thaliana. Mouse-ear cress. Organism_taxid: 3702. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PDB file)
Resolution:
2.60Å     R-factor:   0.208     R-free:   0.248
Authors: C.Mas-Droux,V.Biou,R.Dumas
Key ref:
C.Mas-Droux et al. (2006). Allosteric threonine synthase. Reorganization of the pyridoxal phosphate site upon asymmetric activation through S-adenosylmethionine binding to a novel site. J Biol Chem, 281, 5188-5196. PubMed id: 16319072 DOI: 10.1074/jbc.M509798200
Date:
27-Sep-05     Release date:   28-Nov-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9S7B5  (THRC1_ARATH) -  Threonine synthase 1, chloroplastic
Seq:
Struc:
 
Seq:
Struc:
526 a.a.
445 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.4.2.3.1  - Threonine synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Threonine Biosynthesis
      Reaction: O-phospho-L-homoserine + H2O = L-threonine + phosphate
O-phospho-L-homoserine
+ H(2)O
=
L-threonine
Bound ligand (Het Group name = TRS)
matches with 60.00% similarity
+ phosphate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plastid   4 terms 
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M509798200 J Biol Chem 281:5188-5196 (2006)
PubMed id: 16319072  
 
 
Allosteric threonine synthase. Reorganization of the pyridoxal phosphate site upon asymmetric activation through S-adenosylmethionine binding to a novel site.
C.Mas-Droux, V.Biou, R.Dumas.
 
  ABSTRACT  
 
Threonine synthase (TS) is a fold-type II pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the ultimate step of threonine synthesis in plants and microorganisms. Unlike the enzyme from microorganisms, plant TS is activated by S-adenosylmethionine (AdoMet). The mechanism of activation has remained unknown up to now. We report here the crystallographic structures of Arabidopsis thaliana TS in complex with PLP (aTS) and with PLP and AdoMet (aTS-AdoMet), which show with atomic detail how AdoMet activates TS. The aTS structure reveals a PLP orientation never previously observed for a type II PLP-dependent enzyme and explains the low activity of plant TS in the absence of its allosteric activator. The aTS-AdoMet structure shows that activation of the enzyme upon AdoMet binding triggers a large reorganization of active site loops in one monomer of the structural dimer and allows the displacement of PLP to its active conformation. Comparison with other TS structures shows that activation of the second monomer may be triggered by substrate binding. This structure also discloses a novel fold for two AdoMet binding sites located at the dimer interface, each site containing two AdoMet effectors bound in tandem. Moreover, aTS-AdoMet is the first structure of an enzyme that uses AdoMet as an allosteric effector.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. Ribbon drawing of the aTS dimer complexed with AdoMet. Ribbons of domain 1, domain 2, domain 3, and swap domain of monomer A are shown in cyan, magenta, green, and orange, respectively. The gray ribbon represents the monomer B. The C-terminal swap domain of each monomer interacts with domain 2 of the other monomer. The co-factor PLP is shown in black sticks. The four AdoMet effectors are shown at the dimer interface in blue (AdoMet 1 and AdoMet 3) or red (AdoMet 2 and AdoMet 4) sticks. All protein representations were done using the program PYMOL (www.pymol.org). SAM, AdoMet.
Figure 2.
FIGURE 2. Active site and PLP orientation. A, interactions of PLP inside the active site of aTS. B, interactions of PLP inside the active site of monomer A of aTS-AdoMet. Domains 2 and 3 are shown in magenta and green, respectively. PLP is shown in orange stick, and the water molecule is represented as a red sphere. Dotted lines show interaction <3.3 Å between PLP and residues of the active site. AdoMet binding induces conformational changes leading to the reorganization of one active site with a PLP orientation similar to that observed in non-allosteric TS. C and D, 2mF[o] - DF[c] electron density maps around the PLP molecules for aTS and aTS-AdoMet monomer A, respectively. Maps are traced at 1 standard deviation.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 5188-5196) copyright 2006.  
  Figures were selected by the author.  
 
 
    Author's comment    
 
  Threonine synthase (TS) is a fold-type II pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the ultimate step of threonine synthesis in plants and micro-organisms. Unlike enzyme from micro-organisms, plant TS is activated by S-adenosylmethionine (AdoMet). The structure of the plant TS without AdoMet reveals a PLP orientation which was never previously observed for a type II PLP-dependent enzyme and explains the low activity of plant TS in absence of AdoMet. The structure of the plant TS with AdoMet shows that AdoMet triggers a large reorganisation of active site loops in only one monomer of the dimer and allows the displacement of PLP to its active orientation observed in other fold-type II PLP-dependent enzymes. The structure with adoMet also discloses two SAM binding sites located at the dimer interface, each site containing two SAM effectors bound in tandem.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20019093 G.Jander, and V.Joshi (2010).
Recent progress in deciphering the biosynthesis of aspartate-derived amino acids in plants.
  Mol Plant, 3, 54-65.  
20186554 V.Joshi, J.G.Joung, Z.Fei, and G.Jander (2010).
Interdependence of threonine, methionine and isoleucine metabolism in plants: accumulation and transcriptional regulation under abiotic stress.
  Amino Acids, 39, 933-947.  
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.  
19640845 M.Goto, T.Yamauchi, N.Kamiya, I.Miyahara, T.Yoshimura, H.Mihara, T.Kurihara, K.Hirotsu, and N.Esaki (2009).
Crystal structure of a homolog of mammalian serine racemase from Schizosaccharomyces pombe.
  J Biol Chem, 284, 25944-25952.
PDB codes: 1wtc 2zr8
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.