PDBsum entry 1bks

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Lyase PDB id
Protein chains
255 a.a. *
392 a.a. *
Waters ×292
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Tryptophan synthase (E.C. from salmonella typhimuri
Structure: Tryptophan synthase. Chain: a. Synonym: tryptophan synthetase. Engineered: yes. Other_details: structure of wild type, holo-enzyme. Tryptophan synthase. Chain: b. Synonym: tryptophan synthetase. Engineered: yes.
Source: Salmonella typhimurium. Organism_taxid: 602. Strain: tb2211. Gene: trpa/trpb/trpc. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.20Å     R-factor:   not given    
Authors: C.C.Hyde
Key ref:
S.Rhee et al. (1996). Exchange of K+ or Cs+ for Na+ induces local and long-range changes in the three-dimensional structure of the tryptophan synthase alpha2beta2 complex. Biochemistry, 35, 4211-4221. PubMed id: 8672457 DOI: 10.1021/bi952506d
10-Jul-98     Release date:   23-Mar-99    
Supersedes: 1wsy
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00929  (TRPA_SALTY) -  Tryptophan synthase alpha chain
268 a.a.
255 a.a.
Protein chain
Pfam   ArchSchema ?
P0A2K1  (TRPB_SALTY) -  Tryptophan synthase beta chain
397 a.a.
392 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/bi952506d Biochemistry 35:4211-4221 (1996)
PubMed id: 8672457  
Exchange of K+ or Cs+ for Na+ induces local and long-range changes in the three-dimensional structure of the tryptophan synthase alpha2beta2 complex.
S.Rhee, K.D.Parris, S.A.Ahmed, E.W.Miles, D.R.Davies.
Monovalent cations activate the pyridoxal phosphate-dependent reactions of tryptophan synthase and affect intersubunit communication in the alpha2beta2 complex. We report refined crystal structures of the tryptophan synthase alpha2beta2 complex from Salmonella typhimurium in the presence of K+ at 2.0 angstrom and of Cs+ at 2.3 angstrom. Comparison of these structures with the recently refined structure in the presence of Na+ shows that each monovalent cation binds at approximately the same position about 8 angstrom from the phosphate of pyridoxal phosphate. Na+ and K+ are coordinated to the carbonyl oxygens of beta Phe-306, beta Ser-308, and beta Gly-232 and to two or one water molecule, respectively. Cs+ is coordinated to the carbonyl oxygens of beta Phe-306, beta Ser-308, beta Gly-232, beta Val-231, beta Gly-268 and beta Leu-304. A second binding site for Cs+ is located in the beta/beta interface on the 2-fold axis with four carbonyl oxygens in the coordination sphere. In addition to local changes in structure close to the cation binding site, a number of long-range changes are observed. The K+ and Cs+ structures differ from the Na+ structure with respect to the positions of beta Asp-305, beta Lys-167, and alpha Asp-56. One unexpected result of this investigation is the movement of the side chains of beta Phe-280 and beta Tyr-279 from a position partially blocking the tunnel in the Na+ structure to a position lining the surface of the tunnel in the K+ and Cs+ structures. The results provide a structural basis for understanding the effects of cations on activity and intersubunit communication.

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.  
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
17951049 S.Mouilleron, and B.Golinelli-Pimpaneau (2007).
Conformational changes in ammonia-channeling glutamine amidotransferases.
  Curr Opin Struct Biol, 17, 653-664.  
16267046 E.Di Cera (2006).
A structural perspective on enzymes activated by monovalent cations.
  J Biol Chem, 281, 1305-1308.  
15869381 D.Davies, and D.Davies (2005).
A quiet life with proteins.
  Annu Rev Biophys Biomol Struct, 34, 1.  
15152000 A.O.Pineda, C.J.Carrell, L.A.Bush, S.Prasad, S.Caccia, Z.W.Chen, F.S.Mathews, and E.Di Cera (2004).
Molecular dissection of Na+ binding to thrombin.
  J Biol Chem, 279, 31842-31853.
PDB codes: 1sfq 1sg8 1sgi 1shh
15117965 F.Schiaretti, S.Bettati, C.Viappiani, and A.Mozzarelli (2004).
pH dependence of tryptophan synthase catalytic mechanism: I. The first stage, the beta-elimination reaction.
  J Biol Chem, 279, 29572-29582.  
15206928 Y.Hioki, K.Ogasahara, S.J.Lee, J.Ma, M.Ishida, Y.Yamagata, Y.Matsuura, M.Ota, M.Ikeguchi, S.Kuramitsu, and K.Yutani (2004).
The crystal structure of the tryptophan synthase beta subunit from the hyperthermophile Pyrococcus furiosus. Investigation of stabilization factors.
  Eur J Biochem, 271, 2624-2635.
PDB code: 1v8z
12939261 A.Osborne, Q.Teng, E.W.Miles, and R.S.Phillips (2003).
Detection of open and closed conformations of tryptophan synthase by 15N-heteronuclear single-quantum coherence nuclear magnetic resonance of bound 1-15N-L-tryptophan.
  J Biol Chem, 278, 44083-44090.  
12799468 R.Amaro, E.Tajkhorshid, and Z.Luthey-Schulten (2003).
Developing an energy landscape for the novel function of a (beta/alpha)8 barrel: ammonia conduction through HisF.
  Proc Natl Acad Sci U S A, 100, 7599-7604.  
14612565 S.Prasad, K.J.Wright, D.Banerjee Roy, L.A.Bush, A.M.Cantwell, and E.Di Cera (2003).
Redesigning the monovalent cation specificity of an enzyme.
  Proc Natl Acad Sci U S A, 100, 13785-13790.  
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
12146963 O.Hur, D.Niks, P.Casino, and M.F.Dunn (2002).
Proton transfers in the beta-reaction catalyzed by tryptophan synthase.
  Biochemistry, 41, 9991.  
12146962 R.M.Harris, and M.F.Dunn (2002).
Intermediate trapping via a conformational switch in the Na(+)-activated tryptophan synthase bienzyme complex.
  Biochemistry, 41, 9982-9990.  
11893063 E.W.Miles (2001).
Tryptophan synthase: a multienzyme complex with an intramolecular tunnel.
  Chem Rec, 1, 140-151.  
11395405 X.Huang, H.M.Holden, and F.M.Raushel (2001).
Channeling of substrates and intermediates in enzyme-catalyzed reactions.
  Annu Rev Biochem, 70, 149-180.  
10702257 A.Mozzarelli, A.Peracchi, B.Rovegno, G.Dalè, G.L.Rossi, and M.F.Dunn (2000).
Effect of pH and monovalent cations on the formation of quinonoid intermediates of the tryptophan synthase alpha(2)beta(2) complex in solution and in the crystal.
  J Biol Chem, 275, 6956-6962.  
10673422 D.Kohls, T.Sulea, E.O.Purisima, R.E.MacKenzie, and A.Vrielink (2000).
The crystal structure of the formiminotransferase domain of formiminotransferase-cyclodeaminase: implications for substrate channeling in a bifunctional enzyme.
  Structure, 8, 35-46.
PDB code: 1qd1
11209753 P.Rondard, and H.Bedouelle (2000).
Mutational scanning of a hairpin loop in the tryptophan synthase beta-subunit implicated in allostery and substrate channeling.
  Biol Chem, 381, 1185-1193.  
10212181 E.W.Miles, S.Rhee, and D.R.Davies (1999).
The molecular basis of substrate channeling.
  J Biol Chem, 274, 12193-12196.  
10531312 H.S.Ro, and E.Wilson Miles (1999).
Catalytic mechanism of the tryptophan synthase alpha(2)beta(2) complex. Effects of pH, isotopic substitution, and allosteric ligands.
  J Biol Chem, 274, 31189-31194.  
10601247 K.D.Schnackerz, C.H.Tai, R.K.Pötsch, and P.F.Cook (1999).
Substitution of pyridoxal 5'-phosphate in D-serine dehydratase from Escherichia coli by cofactor analogues provides information on cofactor binding and catalysis.
  J Biol Chem, 274, 36935-36943.  
9562556 D.T.Gallagher, G.L.Gilliland, G.Xiao, J.Zondlo, K.E.Fisher, D.Chinchilla, and E.Eisenstein (1998).
Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase.
  Structure, 6, 465-475.
PDB code: 1tdj
9478945 J.Davoodi, P.M.Drown, R.K.Bledsoe, R.Wallin, G.D.Reinhart, and S.M.Hutson (1998).
Overexpression and characterization of the human mitochondrial and cytosolic branched-chain aminotransferases.
  J Biol Chem, 273, 4982-4989.  
9914248 J.L.Smith (1998).
Glutamine PRPP amidotransferase: snapshots of an enzyme in action.
  Curr Opin Struct Biol, 8, 686-694.  
9914259 J.N.Jansonius (1998).
Structure, evolution and action of vitamin B6-dependent enzymes.
  Curr Opin Struct Biol, 8, 759-769.  
9837895 K.D.Schnackerz, and A.Mozzarelli (1998).
Plasticity of the tryptophan synthase active site probed by 31P NMR spectroscopy.
  J Biol Chem, 273, 33247-33253.  
9856999 P.Rondard, and H.Bedouelle (1998).
A mutational approach shows similar mechanisms of recognition for the isolated and integrated versions of a protein epitope.
  J Biol Chem, 273, 34753-34759.  
9535826 S.Rhee, E.W.Miles, and D.R.Davies (1998).
Cryo-crystallography of a true substrate, indole-3-glycerol phosphate, bound to a mutant (alphaD60N) tryptophan synthase alpha2beta2 complex reveals the correct orientation of active site alphaGlu49.
  J Biol Chem, 273, 8553-8555.
PDB codes: 1a5a 1a5b
9370373 D.Madern, and G.Zaccai (1997).
Stabilisation of halophilic malate dehydrogenase from Haloarcula marismortui by divalent cations -- effects of temperature, water isotope, cofactor and pH.
  Eur J Biochem, 249, 607-611.  
9428713 L.Ramírez-Silva, J.Oria, A.Gómez-Puyou, and M.Tuena de Gómez-Puyou (1997).
The contribution of water to the selectivity of pyruvate kinase for Na+ and K+.
  Eur J Biochem, 250, 583-589.  
9020588 P.Pan, E.Woehl, and M.F.Dunn (1997).
Protein architecture, dynamics and allostery in tryptophan synthase channeling.
  Trends Biochem Sci, 22, 22-27.  
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.