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PDBsum entry 2clk

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
2clk
Jmol
Contents
Protein chains
267 a.a. *
390 a.a. *
Ligands
G3H
PLP
Metals
_NA
Waters ×533
* Residue conservation analysis
PDB id:
2clk
Name: Lyase
Title: Tryptophan synthase in complex with d-glyceraldehyde 3- phosphate (g3p)
Structure: Tryptophan synthase alpha chain. Chain: a. Engineered: yes. Tryptophan synthase beta chain. Chain: b. Engineered: yes. Other_details: internal aldimine formed between b-k87 and c4 of pyridoxal-5'-phosphate
Source: Salmonella typhimurium. Organism_taxid: 602. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.50Å     R-factor:   0.180     R-free:   0.202
Authors: H.Ngo,R.Harris,N.Kimmich,P.Casino,D.Niks,L.Blumenstein, T.R.Barends,V.Kulik,M.Weyand,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 DOI: 10.1021/bi700385f
Date:
27-Apr-06     Release date:   12-Jun-07    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00929  (TRPA_SALTY) -  Tryptophan synthase alpha chain
Seq:
Struc:
268 a.a.
267 a.a.*
Protein chain
Pfam   ArchSchema ?
P0A2K1  (TRPB_SALTY) -  Tryptophan synthase beta chain
Seq:
Struc:
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.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 = G3H)
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  

 

 
    reference    
 
 
DOI no: 10.1021/bi700385f 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.
 
  ABSTRACT  
 
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.  
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.