Gene Symbol: trpA
Description: tryptophan synthase subunit alpha
Species: Salmonella typhimurium LT2

Top Publications

  1. Axe J, Yezdimer E, O Rourke K, Kerstetter N, You W, Chang C, et al. Amino acid networks in a (?/?)? barrel enzyme change during catalytic turnover. J Am Chem Soc. 2014;136:6818-21 pubmed publisher
    ..These findings demonstrate that amino acid networks, similar to those studied here, are likely important for coordinating structural changes necessary for enzyme function and regulation...
  2. Schneider T, Gerhardt E, Lee M, Liang P, Anderson K, Schlichting I. Loop closure and intersubunit communication in tryptophan synthase. Biochemistry. 1998;37:5394-406 pubmed
    ..These findings provide a structural basis for understanding the allosteric properties of tryptophan synthase. ..
  3. Blumenstein L, Domratcheva T, Niks D, Ngo H, Seidel R, Dunn M, et al. BetaQ114N and betaT110V mutations reveal a critically important role of the substrate alpha-carboxylate site in the reaction specificity of tryptophan synthase. Biochemistry. 2007;46:14100-16 pubmed
    ..This study reveals a new layer of structure-function interactions essential for reaction specificity in tryptophan synthase. ..
  4. Schneider W, Nichols B, Yanofsky C. Procedure for production of hybrid genes and proteins and its use in assessing significance of amino acid differences in homologous tryptophan synthetase alpha polypeptides. Proc Natl Acad Sci U S A. 1981;78:2169-73 pubmed
    Hybrid tryptophan synthetase alpha and beta polypeptides were produced by genetic recombination between the trpB--trpA regions of Escherichia coli and Salmonella typhimurium contained on compatible, multicopy plasmids...
  5. Kulik V, Hartmann E, Weyand M, Frey M, Gierl A, Niks D, et al. On the structural basis of the catalytic mechanism and the regulation of the alpha subunit of tryptophan synthase from Salmonella typhimurium and BX1 from maize, two evolutionarily related enzymes. J Mol Biol. 2005;352:608-20 pubmed publisher
    ..The latter is caused by a substitution of the residues that stabilize the inactive conformation in TRPS...
  6. Kulik V, Weyand M, Seidel R, Niks D, Arac D, Dunn M, et al. On the role of alphaThr183 in the allosteric regulation and catalytic mechanism of tryptophan synthase. J Mol Biol. 2002;324:677-90 pubmed
    ..The structural basis for the reduced alpha-activity has its origins in the missing hydrogen bond between alphaThr183 and the catalytic residue, alphaAsp60...
  7. Weyand M, Schlichting I. Crystal structure of wild-type tryptophan synthase complexed with the natural substrate indole-3-glycerol phosphate. Biochemistry. 1999;38:16469-80 pubmed
    ..These findings form the structural basis for the information transfer from the alpha- to the beta-subunit and may explain the affinity increase of the beta-active site for serine upon IGP binding. ..
  8. Ngo H, Harris R, Kimmich N, Casino P, Niks D, Blumenstein L, et al. Synthesis and characterization of allosteric probes of substrate channeling in the tryptophan synthase bienzyme complex. Biochemistry. 2007;46:7713-27 pubmed publisher
    ..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...
  9. Rhee S, Parris K, Ahmed S, Miles E, Davies D. 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. 1996;35:4211-21 pubmed publisher
    ..The results provide a structural basis for understanding the effects of cations on activity and intersubunit communication...

More Information


  1. Rhee S, Parris K, Hyde C, Ahmed S, Miles E, Davies D. Crystal structures of a mutant (betaK87T) tryptophan synthase alpha2beta2 complex with ligands bound to the active sites of the alpha- and beta-subunits reveal ligand-induced conformational changes. Biochemistry. 1997;36:7664-80 pubmed publisher
    ..These large-scale changes, the closure of loop 6, and the movements of a small number of side chains in the alpha-beta interaction site provide a structural base for interpreting the allosteric properties of tryptophan synthase...
  2. Rhee S, Miles E, Mozzarelli A, Davies D. Cryocrystallography and microspectrophotometry of a mutant (alpha D60N) tryptophan synthase alpha 2 beta 2 complex reveals allosteric roles of alpha Asp60. Biochemistry. 1998;37:10653-9 pubmed publisher
    ..These observations show that alpha Asp60 plays important roles in the closure of loop 6 and in allosteric communication between the alpha- and beta-subunits...
  3. Ahmed S, Miles E, Davies D. Crystallization and preliminary X-ray crystallographic data of the tryptophan synthase alpha 2 beta 2 complex from Salmonella typhimurium. J Biol Chem. 1985;260:3716-8 pubmed
    ..typhimurium alpha, holo-beta 2, and apo-beta 2 subunits do not crystallize under these conditions nor do the alpha 2 beta 2 complex or the alpha- or holo-beta 2 subunits from Escherichia coli or from an interspecies hybrid. ..
  4. Ngo H, Kimmich N, Harris R, Niks D, Blumenstein L, Kulik V, et al. Allosteric regulation of substrate channeling in tryptophan synthase: modulation of the L-serine reaction in stage I of the beta-reaction by alpha-site ligands. Biochemistry. 2007;46:7740-53 pubmed publisher
    ..Harris, R., Kimmich, N., Casino, P., Niks, D., Blumenstein, L., Barends, T. R., Kulik, V., Weyand, M., Schlichting, I., and Dunn, M. F. (2007) Biochemistry 46, 7713-7727]...
  5. Weyand M, Schlichting I, Herde P, Marabotti A, Mozzarelli A. Crystal structure of the beta Ser178--> Pro mutant of tryptophan synthase. A "knock-out" allosteric enzyme. J Biol Chem. 2002;277:10653-60 pubmed
    ..This effects the equilibrium between active and inactive conformations of the alpha-active site, altering k(cat) and K(m), and forms the structural basis for the missing allosteric communication between the alpha- and beta-subunits. ..
  6. Hilario E, Caulkins B, Huang Y, You W, Chang C, Mueller L, et al. Visualizing the tunnel in tryptophan synthase with crystallography: Insights into a selective filter for accommodating indole and rejecting water. Biochim Biophys Acta. 2016;1864:268-279 pubmed publisher
    ..Flexible docking studies and MD simulations confirm that the dynamic behavior of βPhe280 allows unhindered transfer of indole through the tunnel, therefore excluding a gating role for this residue. ..
  7. Nichols B, Yanofsky C. Nucleotide sequences of trpA of Salmonella typhimurium and Escherichia coli: an evolutionary comparison. Proc Natl Acad Sci U S A. 1979;76:5244-8 pubmed
    The complete nucleotide sequences of trpA of Salmonella typhimurium and Escherichia coli were determined. The nucleotide sequences are 24.8% divergent, compared with amino acid sequence divergence of 14.9%...
  8. Hyde C, Miles E. The tryptophan synthase multienzyme complex: exploring structure-function relationships with X-ray crystallography and mutagenesis. Biotechnology (N Y). 1990;8:27-32 pubmed
    ..Recombinant DNA technology should also be useful in analyzing protein-protein interaction, protein folding and the channeling phenomenon. ..
  9. Weyand M, Schlichting I, Marabotti A, Mozzarelli A. Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase. J Biol Chem. 2002;277:10647-52 pubmed
    ..In this case, closure of loop alphaL6 is no longer observed, in agreement with its functioning only as an inhibitor of the alpha-subunit reaction. ..
  10. Rhee S, Miles E, Davies D. 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. 1998;273:8553-5 pubmed
    ..Our results demonstrate how cryo-crystallography and mutagenesis can provide insight into enzyme mechanism. ..
  11. Crawford I, Nichols B, Yanofsky C. Nucleotide sequence of the trpB gene in Escherichia coli and Salmonella typhimurium. J Mol Biol. 1980;142:489-502 pubmed
  12. Li S, Yanofsky C. Amino acid sequence studies with the tryptophan synthetase chain of Salmonella typhimurium. J Biol Chem. 1973;248:1830-6 pubmed
  13. Weyand M, Schlichting I. Structural basis for the impaired channeling and allosteric inter-subunit communication in the beta A169L/beta C170W mutant of tryptophan synthase. J Biol Chem. 2000;275:41058-63 pubmed
    ..The proposed structural dissection of the effects of each single mutation in the betaA169L/betaC170W mutant would explain the very different kinetics of this mutant and betaC170F. ..
  14. Sachpatzidis A, deAlwis C, Lubetsky J, Liang P, Anderson K, Lolis E. Crystallographic studies of phosphonate-based alpha-reaction transition-state analogues complexed to tryptophan synthase. Biochemistry. 1999;38:12665-74 pubmed
    ..Implications for the mechanism of catalysis as well as directions for more potent inhibitors are discussed. ..
  15. Lu Z, Nagata S, McPhie P, Miles E. Lysine 87 in the beta subunit of tryptophan synthase that forms an internal aldimine with pyridoxal phosphate serves critical roles in transimination, catalysis, and product release. J Biol Chem. 1993;268:8727-34 pubmed
  16. Hyde C, Ahmed S, Padlan E, Miles E, Davies D. Three-dimensional structure of the tryptophan synthase alpha 2 beta 2 multienzyme complex from Salmonella typhimurium. J Biol Chem. 1988;263:17857-71 pubmed