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On the role of alphaThr183 in the allosteric regulation and catalytic mechanism of tryptophan synthase.

Kulik V, Weyand M, Seidel R, Niks D, Arac D, Dunn MF, Schlichting I
J Mol Biol 324 677-90 (2002)
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Cited: 32 times
EuropePMC logo PMID: 12460570

Abstract

The catalytic activity and substrate channeling of the pyridoxal 5'-phosphate-dependent tryptophan synthase alpha(2)beta(2) complex is regulated by allosteric interactions that modulate the switching of the enzyme between open, low activity and closed, high activity states during the catalytic cycle. The highly conserved alphaThr183 residue is part of loop alphaL6 and is located next to the alpha-active site and forms part of the alpha-beta subunit interface. The role of the interactions of alphaThr183 in alpha-site catalysis and allosteric regulation was investigated by analyzing the kinetics and crystal structures of the isosteric mutant alphaThr183Val. The mutant displays strongly impaired allosteric alpha-beta communication, and the catalytic activity of the alpha-reaction is reduced one hundred fold, whereas the beta-activity is not affected. The structural work establishes that the basis for the missing inter-subunit signaling is the lack of loop alphaL6 closure even in the presence of the alpha-subunit ligands, 3-indolyl-D-glycerol 3'-phosphate, or 3-indolylpropanol 3'-phosphate. The structural basis for the reduced alpha-activity has its origins in the missing hydrogen bond between alphaThr183 and the catalytic residue, alphaAsp60.

Articles - 1k8x mentioned but not cited (1)

  1. Computational Analysis on the Allostery of Tryptophan Synthase: Relationship between α/β-Ligand Binding and Distal Domain Closure. Ito S, Yagi K, Sugita Y. J Phys Chem B 126 3300-3308 (2022)


Reviews citing this publication (5)

  1. Tryptophan synthase: the workings of a channeling nanomachine. Dunn MF, Niks D, Ngo H, Barends TR, Schlichting I. Trends Biochem Sci 33 254-264 (2008)
  2. Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex. Dunn MF. Arch Biochem Biophys 519 154-166 (2012)
  3. Influence of the tryptophan-indole-IFNγ axis on human genital Chlamydia trachomatis infection: role of vaginal co-infections. Aiyar A, Quayle AJ, Buckner LR, Sherchand SP, Chang TL, Zea AH, Martin DH, Belland RJ. Front Cell Infect Microbiol 4 72 (2014)
  4. Tryptophan synthase: a mine for enzymologists. Raboni S, Bettati S, Mozzarelli A. Cell Mol Life Sci 66 2391-2403 (2009)
  5. Allosteric regulation of substrate channeling: Salmonella typhimurium tryptophan synthase. Ghosh RK, Hilario E, Chang CA, Mueller LJ, Dunn MF. Front Mol Biosci 9 923042 (2022)

Articles citing this publication (26)

  1. Structure and mechanistic implications of a tryptophan synthase quinonoid intermediate. Barends TR, Domratcheva T, Kulik V, Blumenstein L, Niks D, Dunn MF, Schlichting I. Chembiochem 9 1024-1028 (2008)
  2. Allostery and substrate channeling in the tryptophan synthase bienzyme complex: evidence for two subunit conformations and four quaternary states. Niks D, Hilario E, Dierkers A, Ngo H, Borchardt D, Neubauer TJ, Fan L, Mueller LJ, Dunn MF. Biochemistry 52 6396-6411 (2013)
  3. Exploring the pyridoxal 5'-phosphate-dependent enzymes. Mozzarelli A, Bettati S. Chem Rec 6 275-287 (2006)
  4. Protonation states of the tryptophan synthase internal aldimine active site from solid-state NMR spectroscopy: direct observation of the protonated Schiff base linkage to pyridoxal-5'-phosphate. Caulkins BG, Bastin B, Yang C, Neubauer TJ, Young RP, Hilario E, Huang YM, Chang CE, Fan L, Dunn MF, Marsella MJ, Mueller LJ. J Am Chem Soc 136 12824-12827 (2014)
  5. 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. Kulik V, Hartmann E, Weyand M, Frey M, Gierl A, Niks D, Dunn MF, Schlichting I. J Mol Biol 352 608-620 (2005)
  6. Tryptophan synthase, an allosteric molecular factory. Barends TR, Dunn MF, Schlichting I. Curr Opin Chem Biol 12 593-600 (2008)
  7. Long-range interactions in the α subunit of tryptophan synthase help to coordinate ligand binding, catalysis, and substrate channeling. Axe JM, Boehr DD. J Mol Biol 425 1527-1545 (2013)
  8. What stabilizes close arginine pairing in proteins? Lee D, Lee J, Seok C. Phys Chem Chem Phys 15 5844-5853 (2013)
  9. Confinement and crowding effects on tryptophan synthase alpha2beta2 complex. Pioselli B, Bettati S, Mozzarelli A. FEBS Lett 579 2197-2202 (2005)
  10. H2r: identification of evolutionary important residues by means of an entropy based analysis of multiple sequence alignments. Merkl R, Zwick M. BMC Bioinformatics 9 151 (2008)
  11. Identification of the geometric requirements for allosteric communication between the alpha- and beta-subunits of tryptophan synthase. Raboni S, Bettati S, Mozzarelli A. J Biol Chem 280 13450-13456 (2005)
  12. Severing of a hydrogen bond disrupts amino acid networks in the catalytically active state of the alpha subunit of tryptophan synthase. Axe JM, O'Rourke KF, Kerstetter NE, Yezdimer EM, Chan YM, Chasin A, Boehr DD. Protein Sci 24 484-494 (2015)
  13. Tryptophan synthase: structure and function of the monovalent cation site. Dierkers AT, Niks D, Schlichting I, Dunn MF. Biochemistry 48 10997-11010 (2009)
  14. The crystal structure of the tryptophan synthase beta subunit from the hyperthermophile Pyrococcus furiosus. Investigation of stabilization factors. Hioki Y, Ogasahara K, Lee SJ, Ma J, Ishida M, Yamagata Y, Matsuura Y, Ota M, Ikeguchi M, Kuramitsu S, Yutani K. Eur J Biochem 271 2624-2635 (2004)
  15. Distinct conformational dynamics and allosteric networks in alpha tryptophan synthase during active catalysis. O'Rourke KF, D'Amico RN, Sahu D, Boehr DD. Protein Sci 30 543-557 (2021)
  16. Sensor domain of histidine kinase KinB of Pseudomonas: a helix-swapped dimer. Tan K, Chhor G, Binkowski TA, Jedrzejczak RP, Makowska-Grzyska M, Joachimiak A. J Biol Chem 289 12232-12244 (2014)
  17. Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB. Michalska K, Wellington S, Maltseva N, Jedrzejczak R, Selem-Mojica N, Rosas-Becerra LR, Barona-Gómez F, Hung DT, Joachimiak A. Protein Sci 30 1904-1918 (2021)
  18. Conservation of the structure and function of bacterial tryptophan synthases. Michalska K, Gale J, Joachimiak G, Chang C, Hatzos-Skintges C, Nocek B, Johnston SE, Bigelow L, Bajrami B, Jedrzejczak RP, Wellington S, Hung DT, Nag PP, Fisher SL, Endres M, Joachimiak A. IUCrJ 6 649-664 (2019)
  19. Generation of a Stand-Alone Tryptophan Synthase α-Subunit by Mimicking an Evolutionary Blueprint. Schupfner M, Busch F, Wysocki VH, Sterner R. Chembiochem 20 2747-2751 (2019)
  20. Mutation of βGln114 to Ala Alters the Stabilities of Allosteric States in Tryptophan Synthase Catalysis. Ghosh RK, Hilario E, Liu V, Wang Y, Niks D, Holmes JB, Sakhrani VV, Mueller LJ, Dunn MF. Biochemistry 60 3173-3186 (2021)
  21. Structures of wild-type and P28L/Y173F tryptophan synthase alpha-subunits from Escherichia coli. Jeong MS, Jeong JK, Lim WK, Jang SB. Biochem Biophys Res Commun 323 1257-1264 (2004)
  22. Backbone assignments and conformational dynamics in the S. typhimurium tryptophan synthase α-subunit from solution-state NMR. Sakhrani VV, Hilario E, Caulkins BG, Hatcher-Skeers ME, Fan L, Dunn MF, Mueller LJ. J Biomol NMR 74 341-354 (2020)
  23. Millisecond Timescale Motions Connect Amino Acid Interaction Networks in Alpha Tryptophan Synthase. O'Rourke KF, Axe JM, D'Amico RN, Sahu D, Boehr DD. Front Mol Biosci 5 92 (2018)
  24. Strategy for cold adaptation of the tryptophan synthase α subunit from the psychrophile Shewanella frigidimarina K14-2: crystal structure and physicochemical properties. Mitsuya D, Tanaka S, Matsumura H, Urano N, Takano K, Ogasahara K, Takehira M, Yutani K, Ishida M. J Biochem 155 73-82 (2014)
  25. Lysine Decarboxylase with an Enhanced Affinity for Pyridoxal 5-Phosphate by Disulfide Bond-Mediated Spatial Reconstitution. Sagong HY, Kim KJ. PLoS One 12 e0170163 (2017)
  26. A molecular characterization of spontaneous frameshift mutagenesis within the trpA gene of Escherichia coli. Hardin A, Villalta CF, Doan M, Jabri M, Chockalingham V, White SJ, Fowler RG. DNA Repair (Amst) 6 177-189 (2007)


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