PDBsum entry 1wbj

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Lyase PDB id
Protein chains
267 a.a. *
390 a.a. *
Waters ×533
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Wildtype tryptophan synthase complexed with glycerol phosphate
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. Expression_system_taxid: 562
Biol. unit: Tetramer (from PDB file)
1.50Å     R-factor:   0.180     R-free:   0.202
Authors: V.Kulik,M.Weyand,I.Schlichting
Key ref:
V.Kulik et al. (2005). On the structural basis of the catalytic mechanism and the regulation of the alpha subunit of tryptophan synthase from Salmonella typhimurium and BX1 from maize, two evolutionarily related enzymes. J Mol Biol, 352, 608-620. PubMed id: 16120446 DOI: 10.1016/j.jmb.2005.07.014
01-Nov-04     Release date:   24-May-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00929  (TRPA_SALTY) -  Tryptophan synthase alpha chain
268 a.a.
267 a.a.*
Protein chain
Pfam   ArchSchema ?
P0A2K1  (TRPB_SALTY) -  Tryptophan synthase beta chain
397 a.a.
390 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

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

Tryptophan Biosynthesis
      Reaction: L-serine + 1-C-(indol-3-yl)glycerol 3-phosphate = L-tryptophan + D-glyceraldehyde 3-phosphate + H2O
+ 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 = PLP) matches with 93.00% 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  


DOI no: 10.1016/j.jmb.2005.07.014 J Mol Biol 352:608-620 (2005)
PubMed id: 16120446  
On the structural basis of the catalytic mechanism and the regulation of the alpha subunit of tryptophan synthase from Salmonella typhimurium and BX1 from maize, two evolutionarily related enzymes.
V.Kulik, E.Hartmann, M.Weyand, M.Frey, A.Gierl, D.Niks, M.F.Dunn, I.Schlichting.
Indole is a reaction intermediate in at least two biosynthetic pathways in maize seedlings. In the primary metabolism, the alpha-subunit (TSA) of the bifunctional tryptophan synthase (TRPS) catalyzes the cleavage of indole 3-glycerol phosphate (IGP) to indole and d-glyceraldehyde 3-phosphate (G3P). Subsequently, indole diffuses through the connecting tunnel to the beta-active site where it is condensed with serine to form tryptophan and water. The maize enzyme, BX1, a homolog of TSA, also cleaves IGP to G3P and indole, and the indole is further converted to 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one, a secondary plant metabolite. BX1 cleaves IGP significantly faster to G3P and indole than does TSA. In line with their different biological functions, these two evolutionary related enzymes differ significantly in their regulatory aspects while catalyzing the same chemistry. Here, the mechanism of IGP cleavage by TSA was analyzed using a novel transition state analogue generated in situ by reaction of 2-aminophenol and G3P. The crystal structure of the complex shows an sp3-hybridized atom corresponding to the C3 position of IGP. The catalytic alphaGlu49 rotates to interact with the sp3-hybridized atom and the 3' hydroxyl group suggesting that it serves both as proton donor and acceptor in the alpha-reaction. The second catalytic residue, alphaAsp60 interacts with the atom corresponding to the indolyl nitrogen, and the catalytically important loop alphaL6 is in the closed, high activity conformation. Comparison of the TSA and TSA-transition state analogue structures with the crystal structure of BX1 suggests that the faster catalytic rate of BX1 may be due to a stabilization of the active conformation: loop alphaL6 is closed and the catalytic glutamate is in the active conformation. The latter is caused by a substitution of the residues that stabilize the inactive conformation in TRPS.
  Selected figure(s)  
Figure 6.
Figure 6. Environment of the catalytic glutamate. (a) In TPRS, aGlu49 has two conformations, an extended active one interacting with the 3'-hydroxyl of IGP and an inactive one with the carboxylate hydrogen bonded with aTyr173. (b) In BX1 (yellow), Glu134 is positioned in the active conformation. Due to a number of substitutions, including Phe253<->aTyr173 and Ile207<->aLeu127, the corresponding inactive conformation seen in TPRS is not energetically favorable in the BX1 structure.
Figure 7.
Figure 7. The conformation of loop aL6 is determined by the position of an arginine residue. (a) In a-TRPS, the guanidinium group of aArg179 lies in the plane of the loop and forms a number of radial interactions. (b) In BX1 the corresponding guanidinium group, Arg266, is tilted out of the ring plane, resulting in only one interaction with the loop. The two guanidinium groups occupy similar positions in space.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 352, 608-620) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21085641 M.Q.Fatmi, and C.E.Chang (2010).
The role of oligomerization and cooperative regulation in protein function: the case of tryptophan synthase.
  PLoS Comput Biol, 6, e1000994.  
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.  
18366663 R.Merkl, and M.Zwick (2008).
H2r: identification of evolutionary important residues by means of an entropy based analysis of multiple sequence alignments.
  BMC Bioinformatics, 9, 151.  
18844775 R.Zhang, B.Wang, J.Ouyang, J.Li, and Y.Wang (2008).
Arabidopsis indole synthase, a homolog of tryptophan synthase alpha, is an enzyme involved in the Trp-independent indole-containing metabolite biosynthesis.
  J Integr Plant Biol, 50, 1070-1077.  
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
18430213 V.Kriechbaumer, L.Weigang, A.Fiesselmann, T.Letzel, M.Frey, A.Gierl, and E.Glawischnig (2008).
Characterisation of the tryptophan synthase alpha subunit in maize.
  BMC Plant Biol, 8, 44.  
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 code is shown on the right.