PDBsum entry 1cw2

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
Protein chains
264 a.a. *
387 a.a. *
Waters ×184
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of the complex of bacterial tryptophan syn the transition state analogue inhibitor 4-(2-hydroxyphenyls butylphosphonic acid
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.
Biol. unit: Tetramer (from PDB file)
2.00Å     R-factor:   0.214     R-free:   0.250
Authors: A.Sachpatzidis,C.Dealwis,J.B.Lubetsky,P.H.Liang,K.S.Anderson
Key ref:
A.Sachpatzidis et al. (1999). Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase. Biochemistry, 38, 12665-12674. PubMed id: 10504236 DOI: 10.1021/bi9907734
25-Aug-99     Release date:   21-Dec-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00929  (TRPA_SALTY) -  Tryptophan synthase alpha chain
268 a.a.
264 a.a.
Protein chain
Pfam   ArchSchema ?
P0A2K1  (TRPB_SALTY) -  Tryptophan synthase beta chain
397 a.a.
387 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
+ H(2)O
      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!
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1021/bi9907734 Biochemistry 38:12665-12674 (1999)
PubMed id: 10504236  
Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase.
A.Sachpatzidis, C.Dealwis, J.B.Lubetsky, P.H.Liang, K.S.Anderson, E.Lolis.
In an effort to use a structure-based approach for the design of new herbicides, the crystal structures of complexes of tryptophan synthase with a series of phosphonate enzyme inhibitors were determined at 2.3 A or higher resolution. These inhibitors were designed to mimic the transition state formed during the alpha-reaction of the enzyme and, as expected, have affinities much greater than that of the natural substrate indole-3-glycerol phosphate or its nonhydrolyzable analogue indole propanol phosphate (IPP). These inhibitors are ortho-substituted arylthioalkylphosphonate derivatives that have an sp(3)-hybridized sulfur atom, designed to mimic the putative tetrahedral transition state at the C3 atom of the indole, and lack the C2 atom to allow for higher conformational flexibility. Overall, the inhibitors bind in a fashion similar to that of IPP. Glu-49 and Phe-212 are the two active site residues whose conformation changes upon inhibitor binding. A very short hydrogen bond between a phosphonate oxygen and the Ser-235 hydroxyl oxygen may be responsible for stabilization of the enzyme-inhibitor complexes. Implications for the mechanism of catalysis as well as directions for more potent inhibitors are discussed.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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.  
11756456 M.Weyand, I.Schlichting, A.Marabotti, and A.Mozzarelli (2002).
Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase.
  J Biol Chem, 277, 10647-10652.
PDB codes: 1k3u 1k7e 1k7f
11756454 M.Weyand, I.Schlichting, P.Herde, A.Marabotti, and A.Mozzarelli (2002).
Crystal structure of the beta Ser178--> Pro mutant of tryptophan synthase. A "knock-out" allosteric enzyme.
  J Biol Chem, 277, 10653-10660.
PDB codes: 1k7x 1k8y 1k8z
11893063 E.W.Miles (2001).
Tryptophan synthase: a multienzyme complex with an intramolecular tunnel.
  Chem Rec, 1, 140-151.  
11297416 E.Weber-Ban, O.Hur, C.Bagwell, U.Banik, L.H.Yang, E.W.Miles, and M.F.Dunn (2001).
Investigation of allosteric linkages in the regulation of tryptophan synthase: the roles of salt bridges and monovalent cations probed by site-directed mutation, optical spectroscopy, and kinetics.
  Biochemistry, 40, 3497-3511.  
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