PDBsum entry 2cll

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
Jmol PyMol
Protein chains
258 a.a. *
394 a.a. *
Waters ×523
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Tryptophan synthase (external aldimine state) in complex with n-(4'-trifluoromethoxybenzenesulfonyl)-2-amino-1- ethylphosphate (f9)
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.
1.60Å     R-factor:   0.217     R-free:   0.245
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). Synthesis and characterization of allosteric probes of substrate channeling in the tryptophan synthase bienzyme complex. Biochemistry, 46, 7713-7727. PubMed id: 17559195
28-Apr-06     Release date:   12-Jun-07    
Go to PROCHECK summary

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

 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 = PLS) matches with 65.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  


Biochemistry 46:7713-7727 (2007)
PubMed id: 17559195  
Synthesis and characterization of allosteric probes of substrate channeling in the tryptophan synthase bienzyme complex.
H.Ngo, R.Harris, N.Kimmich, P.Casino, D.Niks, L.Blumenstein, T.R.Barends, V.Kulik, M.Weyand, I.Schlichting, M.F.Dunn.
Allosteric interactions regulate substrate channeling in Salmonella typhimurium tryptophan synthase. The channeling of indole between the alpha- and beta-sites via the interconnecting 25 A tunnel is regulated by allosteric signaling arising from binding of ligand to the alpha-site, and covalent reaction of l-Ser at the beta-site. This signaling switches the alpha- and beta-subunits between open conformations of low activity and closed conformations of high activity. Our objective is to synthesize and characterize new classes of alpha-site ligands (ASLs) that mimic the binding of substrates, 3-indole-d-glycerol 3'-phosphate (IGP) or d-glyceraldehyde 3-phosphate (G3P), for use in the investigation of alpha-site-beta-site interactions. The new synthesized IGP analogues contain an aryl group linked to an O-phosphoethanolamine moiety through amide, sulfonamide, or thiourea groups. The G3P analogue, thiophosphoglycolohydroxamate, contains a hydroxamic acid group linked to a thiophosphate moiety. Crystal structures of the internal aldimine complexed with G3P and with three of the new ASLs are presented. These structural and solution studies of the ASL complexes with the internal aldimine form of the enzyme establish the following. (1) ASL binding occurs with high specificity and relatively high affinities at the alpha-site. (2) Binding of the new ASLs slows the entry of indole analogues into the beta-site by blocking the tunnel opening at the alpha-site. (3) ASL binding stabilizes the closed conformations of the beta-subunit for the alpha-aminoacrylate and quinonoid forms of the enzyme. (4) The new ASLs exhibit allosteric properties that parallel the behaviors of IGP and G3P.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20602244 E.Tolonen, B.Bueno, S.Kulshreshta, P.Cieplak, M.Argáez, L.Velázquez, and B.Stec (2011).
Allosteric transition and binding of small molecule effectors causes curvature change in central β-sheets of selected enzymes.
  J Mol Model, 17, 899-911.  
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.  
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.  
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