PDBsum entry 1a5s

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Complex (lyase/inhibitor) PDB id
Protein chains
258 a.a. *
387 a.a. *
Waters ×116
* Residue conservation analysis
PDB id:
Name: Complex (lyase/inhibitor)
Title: Crystal structure of wild-type tryptophan synthase complexed fluoroindole propanol phosphate and l-ser bound as amino ac the beta site
Structure: Tryptophan synthase (alpha chain). Chain: a. Engineered: yes. Tryptophan synthase (beta chain). Chain: b. Engineered: yes
Source: Salmonella typhimurium. Organism_taxid: 602. Cell_line: cb149. Gene: trpa/trpb. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.30Å     R-factor:   0.177     R-free:   0.247
Authors: T.R.Schneider,E.Gerhardt,M.Lee,P.-H.Liang,K.S.Anderson,I.Sch
Key ref:
T.R.Schneider et al. (1998). Loop closure and intersubunit communication in tryptophan synthase. Biochemistry, 37, 5394-5406. PubMed id: 9548921 DOI: 10.1021/bi9728957
17-Feb-98     Release date:   30-Mar-99    
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.
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
Bound ligand (Het Group name = SER)
matches with 85.71% similarity
1-C-(indol-3-yl)glycerol 3-phosphate
Bound ligand (Het Group name = FIP)
matches with 85.00% similarity
= 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/bi9728957 Biochemistry 37:5394-5406 (1998)
PubMed id: 9548921  
Loop closure and intersubunit communication in tryptophan synthase.
T.R.Schneider, E.Gerhardt, M.Lee, P.H.Liang, K.S.Anderson, I.Schlichting.
Crystal structures of wild-type tryptophan synthase alpha2beta2 complexes from Salmonella typhimurium were determined to investigate the mechanism of allosteric activation of the alpha-reaction by the aminoacrylate intermediate formed at the beta-active site. Using a flow cell, the aminoacrylate (A-A) intermediate of the beta-reaction () was generated in the crystal under steady state conditions in the presence of serine and the alpha-site inhibitor 5-fluoroindole propanol phosphate (F-IPP). A model for the conformation of the Schiff base between the aminoacrylate and the beta-subunit cofactor pyridoxal phosphate (PLP) is presented. The structure is compared with structures of the enzyme determined in the absence (TRPS) and presence (TRPSF-IPP) of F-IPP. A detailed model for binding of F-IPP to the alpha-subunit is presented. In contrast to findings by Hyde et al. [(1988) J. Biol. Chem. 263,17857-17871] and Rhee et al. [(1997) Biochemistry 36, 7664-7680], we find that the presence of an alpha-site alone ligand is sufficient for loop alphaL6 closure atop the alpha-active site. Part of this loop, alphaThr183, is important not only for positioning the catalytic alphaAsp60 but also for coordinating the concomitant ordering of loop alphaL2 upon F-IPP binding. On the basis of the three structures, a pathway for communication between the alpha- and beta-active sites has been established. The central element of this pathway is a newly defined rigid, but movable, domain that on one side interacts with the alpha-subunit via loop alphaL2 and on the other side with the beta-active site. These findings provide a structural basis for understanding the allosteric properties of tryptophan synthase.

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
21081698 M.Koutmos, O.Kabil, J.L.Smith, and R.Banerjee (2010).
Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine {beta}-synthase.
  Proc Natl Acad Sci U S A, 107, 20958-20963.
PDB codes: 3pc2 3pc3 3pc4
19387555 S.Raboni, S.Bettati, and A.Mozzarelli (2009).
Tryptophan synthase: a mine for enzymologists.
  Cell Mol Life Sci, 66, 2391-2403.  
18275083 B.C.Lee, K.Park, and D.Kim (2008).
Analysis of the residue-residue coevolution network and the functionally important residues in proteins.
  Proteins, 72, 863-872.  
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.  
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
17411433 J.B.Pereira-Leal, E.D.Levy, C.Kamp, and S.A.Teichmann (2007).
Evolution of protein complexes by duplication of homomeric interactions.
  Genome Biol, 8, R51.  
17922651 P.V.Vrzheshch (2007).
Steady-state kinetics of bifunctional enzymes. Taking into account kinetic hierarchy of fast and slow catalytic cycles in a generalized model.
  Biochemistry (Mosc), 72, 936-943.  
17425797 R.Merkl (2007).
Modelling the evolution of the archeal tryptophan synthase.
  BMC Evol Biol, 7, 59.  
17567578 R.Schnell, W.Oehlmann, M.Singh, and G.Schneider (2007).
Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex.
  J Biol Chem, 282, 23473-23481.
PDB codes: 2q3b 2q3c 2q3d
16636277 E.S.Radisky, J.M.Lee, C.J.Lu, and D.E.Koshland (2006).
Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates.
  Proc Natl Acad Sci U S A, 103, 6835-6840.
PDB codes: 2age 2agg 2agi 2ah4
16132097 B.Adams, K.Lowpetch, F.Thorndycroft, S.M.Whyte, and D.W.Young (2005).
Stereochemistry of reactions of the inhibitor/substrates L- and D-beta-chloroalanine with beta-mercaptoethanol catalysed by L-aspartate aminotransferase and D-amino acid aminotransferase respectively.
  Org Biomol Chem, 3, 3357-3364.  
15691828 S.Raboni, S.Bettati, and A.Mozzarelli (2005).
Identification of the geometric requirements for allosteric communication between the alpha- and beta-subunits of tryptophan synthase.
  J Biol Chem, 280, 13450-13456.  
15044726 B.Pioselli, S.Bettati, T.V.Demidkina, L.N.Zakomirdina, R.S.Phillips, and A.Mozzarelli (2004).
Tyrosine phenol-lyase and tryptophan indole-lyase encapsulated in wet nanoporous silica gels: Selective stabilization of tertiary conformations.
  Protein Sci, 13, 913-924.  
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.  
12643278 K.Ogasahara, M.Ishida, and K.Yutani (2003).
Stimulated interaction between and subunits of tryptophan synthase from hyperthermophile enhances its thermal stability.
  J Biol Chem, 278, 8922-8928.  
12952961 R.Omi, M.Goto, I.Miyahara, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2003).
Crystal structures of threonine synthase from Thermus thermophilus HB8: conformational change, substrate recognition, and mechanism.
  J Biol Chem, 278, 46035-46045.
PDB codes: 1uim 1uin 1uiq 1v7c
14596599 T.Yamada, J.Komoto, Y.Takata, H.Ogawa, H.C.Pitot, and F.Takusagawa (2003).
Crystal structure of serine dehydratase from rat liver.
  Biochemistry, 42, 12854-12865.
PDB codes: 1pwe 1pwh
12011099 C.Fehlner-Gardiner, C.Roshick, J.H.Carlson, S.Hughes, R.J.Belland, H.D.Caldwell, and G.McClarty (2002).
Molecular basis defining human Chlamydia trachomatis tissue tropism. A possible role for tryptophan synthase.
  J Biol Chem, 277, 26893-26903.  
  11806827 G.Xie, C.Forst, C.Bonner, and R.A.Jensen (2002).
Significance of two distinct types of tryptophan synthase beta chain in Bacteria, Archaea and higher plants.
  Genome Biol, 3, RESEARCH0004.  
11756443 M.Garrido-Franco, S.Ehlert, A.Messerschmidt, S.Marinkovic', R.Huber, B.Laber, G.P.Bourenkov, and T.Clausen (2002).
Structure and function of threonine synthase from yeast.
  J Biol Chem, 277, 12396-12405.
PDB code: 1kl7
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
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.  
11756459 S.Hettwer, and R.Sterner (2002).
A novel tryptophan synthase beta-subunit from the hyperthermophile Thermotoga maritima. Quaternary structure, steady-state kinetics, and putative physiological role.
  J Biol Chem, 277, 8194-8201.  
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.  
11483494 M.Meier, M.Janosik, V.Kery, J.P.Kraus, and P.Burkhard (2001).
Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein.
  EMBO J, 20, 3910-3916.
PDB code: 1jbq
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.  
10679381 G.A.Petsko, and D.Ringe (2000).
Observation of unstable species in enzyme-catalyzed transformations using protein crystallography.
  Curr Opin Chem Biol, 4, 89-94.  
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
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.  
10818348 T.R.Schneider (2000).
Objective comparison of protein structures: error-scaled difference distance matrices.
  Acta Crystallogr D Biol Crystallogr, 56, 714-721.  
11029579 X.F.Tang, S.Ezaki, H.Atomi, and T.Imanaka (2000).
Biochemical analysis of a thermostable tryptophan synthase from a hyperthermophilic archaeon.
  Eur J Biochem, 267, 6369-6377.  
10769125 Y.X.Fan, P.McPhie, and E.W.Miles (2000).
Regulation of tryptophan synthase by temperature, monovalent cations, and an allosteric ligand. Evidence from Arrhenius plots, absorption spectra, and primary kinetic isotope effects.
  Biochemistry, 39, 4692-4703.  
10212181 E.W.Miles, S.Rhee, and D.R.Davies (1999).
The molecular basis of substrate channeling.
  J Biol Chem, 274, 12193-12196.  
10353822 E.Woehl, and M.F.Dunn (1999).
Mechanisms of monovalent cation action in enzyme catalysis: the first stage of the tryptophan synthase beta-reaction.
  Biochemistry, 38, 7118-7130.  
10353823 E.Woehl, and M.F.Dunn (1999).
Mechanisms of monovalent cation action in enzyme catalysis: the tryptophan synthase alpha-, beta-, and alpha beta-reactions.
  Biochemistry, 38, 7131-7141.  
10593940 H.S.Ro, and E.W.Miles (1999).
Structure and function of the tryptophan synthase alpha(2)beta(2) complex. Roles of beta subunit histidine 86.
  J Biol Chem, 274, 36439-36445.  
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.  
10090734 I.Bahar, and R.L.Jernigan (1999).
Cooperative fluctuations and subunit communication in tryptophan synthase.
  Biochemistry, 38, 3478-3490.  
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.  
10600108 M.Weyand, and I.Schlichting (1999).
Crystal structure of wild-type tryptophan synthase complexed with the natural substrate indole-3-glycerol phosphate.
  Biochemistry, 38, 16469-16480.
PDB codes: 1qop 1qoq
10387029 Y.X.Fan, P.McPhie, and E.W.Miles (1999).
Guanidine hydrochloride exerts dual effects on the tryptophan synthase alpha 2 beta 2 complex as a cation activator and as a modulator of the active site conformation.
  Biochemistry, 38, 7881-7890.  
9818266 B.L.Stoddard (1998).
New results using Laue diffraction and time-resolved crystallography.
  Curr Opin Struct Biol, 8, 612-618.  
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.  
9692955 S.Rhee, E.W.Miles, A.Mozzarelli, and D.R.Davies (1998).
Cryocrystallography and microspectrophotometry of a mutant (alpha D60N) tryptophan synthase alpha 2 beta 2 complex reveals allosteric roles of alpha Asp60.
  Biochemistry, 37, 10653-10659.
PDB code: 1beu
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.