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PDBsum entry 2j9x

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
2j9x
Jmol
Contents
Protein chains
264 a.a. *
395 a.a. *
Ligands
G3P
P1T
DMS ×3
Metals
_CS ×3
Waters ×418
* Residue conservation analysis
PDB id:
2j9x
Name: Lyase
Title: Tryptophan synthase in complex with gp, alpha-d,l-glycerol- phosphate, cs, ph6.5 - alpha aminoacrylate form - (gp)e(a- a)
Structure: Tryptophan synthase alpha chain. Chain: a. Engineered: yes. Tryptophan synthase beta chain. Chain: b. Engineered: yes
Source: Salmonella typhimurium. Organism_taxid: 602. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.215     R-free:   0.240
Authors: H.Ngo,N.Kimmich,R.Harris,D.Niks,L.Blumenstein,V.Kulik, T.R.Barends,I.Schlichting,M.F.Dunn
Key ref: H.Ngo et al. (2007). Allosteric regulation of substrate channeling in tryptophan synthase: modulation of the L-serine reaction in stage I of the beta-reaction by alpha-site ligands. Biochemistry, 46, 7740-7753. PubMed id: 17559232
Date:
16-Nov-06     Release date:   26-Jun-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00929  (TRPA_SALTY) -  Tryptophan synthase alpha chain
Seq:
Struc:
268 a.a.
264 a.a.
Protein chain
Pfam   ArchSchema ?
P0A2K1  (TRPB_SALTY) -  Tryptophan synthase beta chain
Seq:
Struc:
397 a.a.
395 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.4.2.1.20  - Tryptophan synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Tryptophan Biosynthesis
      Reaction: L-serine + 1-C-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + D-glyceraldehyde 3-phosphate + H2O
L-serine
+ 1-C-(indol-3-yl)glycerol 3-phosphate
= L-tryptophan
+
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = G3P)
corresponds exactly
+ H(2)O
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = P1T) matches with 68.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
Biochemistry 46:7740-7753 (2007)
PubMed id: 17559232  
 
 
Allosteric regulation of substrate channeling in tryptophan synthase: modulation of the L-serine reaction in stage I of the beta-reaction by alpha-site ligands.
H.Ngo, N.Kimmich, R.Harris, D.Niks, L.Blumenstein, V.Kulik, T.R.Barends, I.Schlichting, M.F.Dunn.
 
  ABSTRACT  
 
In the tryptophan synthase bienzyme complex, indole produced by substrate cleavage at the alpha-site is channeled to the beta-site via a 25 A long tunnel. Within the beta-site, indole and l-Ser react with pyridoxal 5'-phosphate in a two-stage reaction to give l-Trp. In stage I, l-Ser forms an external aldimine, E(Aex1), which converts to the alpha-aminoacrylate aldimine, E(A-A). Formation of E(A-A) at the beta-site activates the alpha-site >30-fold. In stage II, indole reacts with E(A-A) to give l-Trp. The binding of alpha-site ligands (ASLs) exerts strong allosteric effects on the reaction of substrates at the beta-site: the distribution of intermediates formed in stage I is shifted in favor of E(A-A), and the binding of ASLs triggers a conformational change in the beta-site to a state with an increased affinity for l-Ser. Here, we compare the behavior of new ASLs as allosteric effectors of stage I with the behavior of the natural product, d-glyceraldehyde 3-phosphate. Rapid kinetics and kinetic isotope effects show these ASLs bind with affinities ranging from micro- to millimolar, and the rate-determining step for conversion of E(Aex1) to E(A-A) is increased by 8-10-fold. To derive a structure-based mechanism for stage I, X-ray structures of both the E(Aex1) and E(A-A) states complexed with the different ASLs were determined and compared with structures of the ASL complexes with the internal aldimine [Ngo, H., Harris, R., Kimmich, N., Casino, P., Niks, D., Blumenstein, L., Barends, T. R., Kulik, V., Weyand, M., Schlichting, I., and Dunn, M. F. (2007) Biochemistry 46, 7713-7727].
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20957111 I.M.de la Fuente (2010).
Quantitative analysis of cellular metabolic dissipative, self-organized structures.
  Int J Mol Sci, 11, 3540-3599.  
20370823 K.Nishio, K.Ogasahara, Y.Morimoto, T.Tsukihara, S.J.Lee, and K.Yutani (2010).
Large conformational changes in the Escherichia coli tryptophan synthase beta(2) subunit upon pyridoxal 5'-phosphate binding.
  FEBS J, 277, 2157-2170.
PDB codes: 2dh5 2dh6
20233374 R.S.Phillips, E.W.Miles, P.McPhie, S.Marchal, R.Lange, G.Holtermann, and R.S.Goody (2010).
Effects of hydrostatic pressure on the conformational equilibrium of tryptophan synthase from Salmonella typhimurium.
  Ann N Y Acad Sci, 1189, 95.  
19387555 S.Raboni, S.Bettati, and A.Mozzarelli (2009).
Tryptophan synthase: a mine for enzymologists.
  Cell Mol Life Sci, 66, 2391-2403.  
18486479 M.F.Dunn, D.Niks, H.Ngo, T.R.Barends, and I.Schlichting (2008).
Tryptophan synthase: the workings of a channeling nanomachine.
  Trends Biochem Sci, 33, 254-264.  
18675375 T.R.Barends, M.F.Dunn, and I.Schlichting (2008).
Tryptophan synthase, an allosteric molecular factory.
  Curr Opin Chem Biol, 12, 593-600.  
18351684 T.R.Barends, T.Domratcheva, V.Kulik, L.Blumenstein, D.Niks, M.F.Dunn, and I.Schlichting (2008).
Structure and mechanistic implications of a tryptophan synthase quinonoid intermediate.
  Chembiochem, 9, 1024-1028.
PDB code: 3cep
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.