3csm Citations

Mechanisms of catalysis and allosteric regulation of yeast chorismate mutase from crystal structures.

Structure 5 1437-52 (1997)
Related entries: 4csm, 5csm

Cited: 37 times
EuropePMC logo PMID: 9384560

Abstract

Background

Chorismate mutase (CM) catalyzes the Claisen rearrangement of chorismate to prephenate, notably the only known enzymatically catalyzed pericyclic reaction in primary metabolism. Structures of the enzyme in complex with an endo-oxabicyclic transition state analogue inhibitor, previously determined for Bacillus subtilis and Escherichia coli CM, provide structural insight into the enzyme mechanism. In contrast to these bacterial CMs, yeast CM is allosterically regulated in two ways: activation by tryptophan and inhibition by tyrosine. Yeast CM exists in two allosteric states, R (active) and t (inactive).

Results

We have determined crystal structures of wild-type yeast CM cocrystallized with tryptophan and an endo-oxabicyclic transition state analogue inhibitor, of wild-type yeast CM co-crystallized with tyrosine and the endo-oxabicyclic transition state analogue inhibitor and of the Thr226-->Ser mutant of yeast CM in complex with tryptophan. Binding of the transition state analogue inhibitor to CM keeps the enzyme in a 'super R' state, even if the inhibitory effector tyrosine is bound to the regulatory site.

Conclusion

The endo-oxabicyclic inhibitor binds to yeast CM in a similar way as it does to the distantly related CM from E. coli. The inhibitor-binding mode supports a mechanism by which polar sidechains of the enzyme bind the substrate in the pseudo-diaxial conformation, which is required for catalytic turnover. A lysine and a protonated glutamate sidechain have a critical role in the stabilization of the transition state of the pericyclic reaction. The allosteric transition from T-->R state is accompanied by a 15 degrees rotation of one of the two subunits relative to the other (where 0 degrees rotation defines the T state). This rotation causes conformational changes at the dimer interface which are transmitted to the active site. An allosteric pathway is proposed to include residues Phe28, Asp24 and Glu23, which move toward the activesite cavity in the T state. In the presence of the transition-state analogue a super R state is formed, which is characterised by a 22 degrees rotation of one subunit relative to the other.

Reviews citing this publication (8)

  1. Epithelial tight junctions in intestinal inflammation. Schulzke JD, Ploeger S, Amasheh M, Fromm A, Zeissig S, Troeger H, Richter J, Bojarski C, Schumann M, Fromm M. Ann. N. Y. Acad. Sci. 1165 294-300 (2009)
  2. Allosteric regulation of catalytic activity: Escherichia coli aspartate transcarbamoylase versus yeast chorismate mutase. Helmstaedt K, Krappmann S, Braus GH. Microbiol. Mol. Biol. Rev. 65 404-21 (2001)
  3. Current developments and challenges in the search for a naturally selected Diels-Alderase. Kim HJ, Ruszczycky MW, Liu HW. Curr Opin Chem Biol 16 124-131 (2012)
  4. Mycobacterium tuberculosis chorismate mutase: A potential target for TB. Khanapur M, Alvala M, Prabhakar M, Shiva Kumar K, Edwin RK, Sri Saranya PS, Patel RK, Bulusu G, Misra P, Pal M. Bioorg. Med. Chem. 25 1725-1736 (2017)
  5. Mycobacterium tuberculosis chorismate mutase: A potential target for TB. Khanapur M, Alvala M, Prabhakar M, Shiva Kumar K, Edwin RK, Sri Saranya PS, Patel RK, Bulusu G, Misra P, Pal M. Bioorg. Med. Chem. 25 1725-1736 (2017)
  6. Current developments and challenges in the search for a naturally selected Diels-Alderase. Kim HJ, Ruszczycky MW, Liu HW. Curr Opin Chem Biol 16 124-131 (2012)
  7. Epithelial tight junctions in intestinal inflammation. Schulzke JD, Ploeger S, Amasheh M, Fromm A, Zeissig S, Troeger H, Richter J, Bojarski C, Schumann M, Fromm M. Ann. N. Y. Acad. Sci. 1165 294-300 (2009)
  8. Allosteric regulation of catalytic activity: Escherichia coli aspartate transcarbamoylase versus yeast chorismate mutase. Helmstaedt K, Krappmann S, Braus GH. Microbiol. Mol. Biol. Rev. 65 404-21 (2001)

Articles citing this publication (29)

  1. Quantifying allosteric effects in proteins. Ming D, Wall ME. Proteins 59 697-707 (2005)
  2. Investigating and Engineering Enzymes by Genetic Selection. Taylor SV, Kast P, Hilvert D. Angew. Chem. Int. Ed. Engl. 40 3310-3335 (2001)
  3. Characterization of the secreted chorismate mutase from the pathogen Mycobacterium tuberculosis. Sasso S, Ramakrishnan C, Gamper M, Hilvert D, Kast P. FEBS J. 272 375-389 (2005)
  4. Substrate conformational transitions in the active site of chorismate mutase: their role in the catalytic mechanism. Guo H, Cui Q, Lipscomb WN, Karplus M. Proc. Natl. Acad. Sci. U.S.A. 98 9032-9037 (2001)
  5. 1.6 A crystal structure of the secreted chorismate mutase from Mycobacterium tuberculosis: novel fold topology revealed. Okvist M, Dey R, Sasso S, Grahn E, Kast P, Krengel U. J. Mol. Biol. 357 1483-1499 (2006)
  6. Structure and function of a complex between chorismate mutase and DAHP synthase: efficiency boost for the junior partner. Sasso S, Okvist M, Roderer K, Gamper M, Codoni G, Krengel U, Kast P. EMBO J. 28 2128-2142 (2009)
  7. Interaction interfaces of protein domains are not topologically equivalent across families within superfamilies: Implications for metabolic and signaling pathways. Rekha N, Machado SM, Narayanan C, Krupa A, Srinivasan N. Proteins 58 339-353 (2005)
  8. Using reaction mechanism to measure enzyme similarity. O'Boyle NM, Holliday GL, Almonacid DE, Mitchell JB. J. Mol. Biol. 368 1484-1499 (2007)
  9. The allosteric mechanism of yeast chorismate mutase: a dynamic analysis. Kong Y, Ma J, Karplus M, Lipscomb WN. J. Mol. Biol. 356 237-247 (2006)
  10. The crystal structure of chorismate lyase shows a new fold and a tightly retained product. Gallagher DT, Mayhew M, Holden MJ, Howard A, Kim KJ, Vilker VL. Proteins 44 304-311 (2001)
  11. Biochemical and structural characterization of the secreted chorismate mutase (Rv1885c) from Mycobacterium tuberculosis H37Rv: an *AroQ enzyme not regulated by the aromatic amino acids. Kim SK, Reddy SK, Nelson BC, Vasquez GB, Davis A, Howard AJ, Patterson S, Gilliland GL, Ladner JE, Reddy PT. J. Bacteriol. 188 8638-8648 (2006)
  12. The solution structure of the regulatory domain of tyrosine hydroxylase. Zhang S, Huang T, Ilangovan U, Hinck AP, Fitzpatrick PF. J. Mol. Biol. 426 1483-1497 (2014)
  13. HARO7 encodes chorismate mutase of the methylotrophic yeast Hansenula polymorpha and is derepressed upon methanol utilization. Krappmann S, Pries R, Gellissen G, Hiller M, Braus GH. J. Bacteriol. 182 4188-4197 (2000)
  14. Structures of open (R) and close (T) states of prephenate dehydratase (PDT)--implication of allosteric regulation by L-phenylalanine. Tan K, Li H, Zhang R, Gu M, Clancy ST, Joachimiak A. J. Struct. Biol. 162 94-107 (2008)
  15. On the generation of catalytic antibodies by transition state analogues. Barbany M, Gutiérrez-de-Terán H, Sanz F, Villà-Freixa J, Villà-Freixa J, Warshel A. Chembiochem 4 277-285 (2003)
  16. Coevolution of transcriptional and allosteric regulation at the chorismate metabolic branch point of Saccharomyces cerevisiae. Krappmann S, Lipscomb WN, Braus GH. Proc. Natl. Acad. Sci. U.S.A. 97 13585-13590 (2000)
  17. Comprehensive analysis of the helix-X-helix motif in soluble proteins. Deville J, Rey J, Chabbert M. Proteins 72 115-135 (2008)
  18. Separation of inhibition and activation of the allosteric yeast chorismate mutase. Schnappauf G, Lipscomb WN, Braus GH. Proc. Natl. Acad. Sci. U.S.A. 95 2868-2873 (1998)
  19. Yeast chorismate mutase in the R state: simulations of the active site. Ma J, Zheng X, Schnappauf G, Braus G, Karplus M, Lipscomb WN. Proc. Natl. Acad. Sci. U.S.A. 95 14640-14645 (1998)
  20. Simultaneous optimization of enzyme activity and quaternary structure by directed evolution. Vamvaca K, Butz M, Walter KU, Taylor SV, Hilvert D. Protein Sci. 14 2103-2114 (2005)
  21. Genetic and biochemical identification of the chorismate mutase from Corynebacterium glutamicum. Li PP, Liu YJ, Liu SJ. Microbiology (Reading, Engl.) 155 3382-3391 (2009)
  22. Mutant characterization and in vivo conditional repression identify aromatic amino acid biosynthesis to be essential for Aspergillus fumigatus virulence. Sasse A, Hamer SN, Amich J, Binder J, Krappmann S. Virulence 7 56-62 (2016)
  23. A proteomic view into infection of greyback canegrubs (Dermolepida albohirtum) by Metarhizium anisopliae. Manalil NS, Junior Te'o VS, Braithwaite K, Brumbley S, Samson P, Nevalainen KM. Curr. Genet. 55 571-581 (2009)
  24. Structural evolution of differential amino acid effector regulation in plant chorismate mutases. Westfall CS, Xu A, Jez JM. J. Biol. Chem. 289 28619-28628 (2014)
  25. Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis. Burschowsky D, van Eerde A, Ökvist M, Kienhöfer A, Kast P, Hilvert D, Krengel U. Proc. Natl. Acad. Sci. U.S.A. 111 17516-17521 (2014)
  26. Refined molecular hinge between allosteric and catalytic domain determines allosteric regulation and stability of fungal chorismate mutase. Helmstaedt K, Heinrich G, Lipscomb WN, Braus GH. Proc. Natl. Acad. Sci. U.S.A. 99 6631-6636 (2002)
  27. Remote Control by Inter-Enzyme Allostery: A Novel Paradigm for Regulation of the Shikimate Pathway. Munack S, Roderer K, Ökvist M, Kamarauskaite J, Sasso S, van Eerde A, Kast P, Krengel U. J. Mol. Biol. 428 1237-1255 (2016)
  28. The importance of chorismate mutase in the biocontrol potential of Trichoderma parareesei. Pérez E, Rubio MB, Cardoza RE, Gutiérrez S, Bettiol W, Monte E, Hermosa R. Front Microbiol 6 1181 (2015)
  29. A novel noncovalent complex of chorismate mutase and DAHP synthase from Mycobacterium tuberculosis: protein purification, crystallization and X-ray diffraction analysis. Okvist M, Sasso S, Roderer K, Kast P, Krengel U. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 65 1048-1052 (2009)


Related citations provided by authors (3)

  1. Crystal Structure of the T State of Allosteric Yeast Chorismate Mutase and Comparison with the R State. Strater N, Hakansson K, Schnappauf G, Braus G, Lipscomb WN Proc. Natl. Acad. Sci. U.S.A. 93 3330- (1996)
  2. Location of the Active Site of Allosteric Chorismate Mutase from Saccharomyces Cerevisiae, and Comments on the Catalytic and Regulatory Mechanisms. Xue Y, Lipscomb WN Proc. Natl. Acad. Sci. U.S.A. 92 10595- (1995)
  3. The Crystal Structure of Allosteric Chorismate Mutase at 2.2-A Resolution. Xue Y, Lipscomb WN, Graf R, Schnappauf G, Braus G Proc. Natl. Acad. Sci. U.S.A. 91 10814- (1994)