3o80 › Citations

Crystal structure of hexokinase KlHxk1 of Kluyveromyces lactis: a molecular basis for understanding the control of yeast hexokinase functions via covalent modification and oligomerization.

Kuettner EB, Kettner K, Keim A, Svergun DI, Volke D, Singer D, Hoffmann R, Müller EC, Otto A, Kriegel TM, Sträter N
J Biol Chem 285 41019-33 (2010)
Related entries: 3o08, 3o1b, 3o1w, 3o4w, 3o5b, 3o6w, 3o8m

Cited: 24 times
EuropePMC logo PMID: 20943665

Abstract

Crystal structures of the unique hexokinase KlHxk1 of the yeast Kluyveromyces lactis were determined using eight independent crystal forms. In five crystal forms, a symmetrical ring-shaped homodimer was observed, corresponding to the physiological dimer existing in solution as shown by small-angle x-ray scattering. The dimer has a head-to-tail arrangement such that the small domain of one subunit interacts with the large domain of the other subunit. Dimer formation requires favorable interactions of the 15 N-terminal amino acids that are part of the large domain with amino acids of the small domain of the opposite subunit, respectively. The head-to-tail arrangement involving both domains of the two KlHxk1 subunits is appropriate to explain the reduced activity of the homodimer as compared with the monomeric enzyme and the influence of substrates and products on dimer formation and dissociation. In particular, the structure of the symmetrical KlHxk1 dimer serves to explain why phosphorylation of conserved residue Ser-15 may cause electrostatic repulsions with nearby negatively charged residues of the adjacent subunit, thereby inducing a dissociation of the homologous dimeric hexokinases KlHxk1 and ScHxk2. Two complex structures of KlHxk1 with bound glucose provide a molecular model of substrate binding to the open conformation and the subsequent classical domain closure motion of yeast hexokinases. The entirety of the novel data extends the current concept of glucose signaling in yeast and complements the induced-fit model by integrating the events of N-terminal phosphorylation and dissociation of homodimeric yeast hexokinases.

Articles - 3o80 mentioned but not cited (2)

  1. Crystal structure of hexokinase KlHxk1 of Kluyveromyces lactis: a molecular basis for understanding the control of yeast hexokinase functions via covalent modification and oligomerization. Kuettner EB, Kettner K, Keim A, Svergun DI, Volke D, Singer D, Hoffmann R, Müller EC, Otto A, Kriegel TM, Sträter N. J Biol Chem 285 41019-41033 (2010)
  2. Novel mutation in hexokinase 2 confers resistance to 2-deoxyglucose by altering protein dynamics. Hellemann E, Walker JL, Lesko MA, Chandrashekarappa DG, Schmidt MC, O'Donnell AF, Durrant JD. PLoS Comput Biol 18 e1009929 (2022)


Reviews citing this publication (1)

  1. Moonlighting Proteins: The Case of the Hexokinases. Rodríguez-Saavedra C, Morgado-Martínez LE, Burgos-Palacios A, King-Díaz B, López-Coria M, Sánchez-Nieto S. Front Mol Biosci 8 701975 (2021)

Articles citing this publication (21)

  1. Involvement of Arabidopsis Hexokinase1 in Cell Death Mediated by Myo-Inositol Accumulation. Bruggeman Q, Prunier F, Mazubert C, de Bont L, Garmier M, Lugan R, Benhamed M, Bergounioux C, Raynaud C, Delarue M. Plant Cell 27 1801-1814 (2015)
  2. HXK1 regulates carbon catabolism, sporulation, fumonisin B₁ production and pathogenesis in Fusarium verticillioides. Kim H, Smith JE, Ridenour JB, Woloshuk CP, Bluhm BH. Microbiology (Reading) 157 2658-2669 (2011)
  3. The catalytic inactivation of the N-half of human hexokinase 2 and structural and biochemical characterization of its mitochondrial conformation. Nawaz MH, Ferreira JC, Nedyalkova L, Zhu H, Carrasco-López C, Kirmizialtin S, Rabeh WM. Biosci Rep 38 BSR20171666 (2018)
  4. Structural insight into activation mechanism of Toxoplasma gondii nucleoside triphosphate diphosphohydrolases by disulfide reduction. Krug U, Zebisch M, Krauss M, Sträter N. J Biol Chem 287 3051-3066 (2012)
  5. Biochemical and structural study of Arabidopsis hexokinase 1. Feng J, Zhao S, Chen X, Wang W, Dong W, Chen J, Shen JR, Liu L, Kuang T. Acta Crystallogr D Biol Crystallogr 71 367-375 (2015)
  6. Polymerization in the actin ATPase clan regulates hexokinase activity in yeast. Stoddard PR, Lynch EM, Farrell DP, Dosey AM, DiMaio F, Williams TA, Kollman JM, Murray AW, Garner EC. Science 367 1039-1042 (2020)
  7. Protein kinase Ymr291w/Tda1 is essential for glucose signaling in saccharomyces cerevisiae on the level of hexokinase isoenzyme ScHxk2 phosphorylation*. Kaps S, Kettner K, Migotti R, Kanashova T, Krause U, Rödel G, Dittmar G, Kriegel TM. J Biol Chem 290 6243-6255 (2015)
  8. Effects of dietary amylose and amylopectin ratio on growth performance, meat quality, postmortem glycolysis and muscle fibre type transformation of finishing pigs. Wang H, Pu J, Chen D, Tian G, Mao X, Yu J, Zheng P, He J, Huang Z, Yu B. Arch Anim Nutr 73 194-207 (2019)
  9. In vivo phosphorylation and in vitro autophosphorylation-inactivation of Kluyveromyces lactis hexokinase KlHxk1. Kettner K, Kuettner EB, Otto A, Lilie H, Golbik RP, Sträter N, Kriegel TM. Biochem Biophys Res Commun 435 313-318 (2013)
  10. Proteomic and functional consequences of hexokinase deficiency in glucose-repressible Kluyveromyces lactis. Mates N, Kettner K, Heidenreich F, Pursche T, Migotti R, Kahlert G, Kuhlisch E, Breunig KD, Schellenberger W, Dittmar G, Hoflack B, Kriegel TM. Mol Cell Proteomics 13 860-875 (2014)
  11. Letter Regulatory Function of Hexokinase 2 in Glucose Signaling in Saccharomyces cerevisiae. Kriegel TM, Kettner K, Rödel G, Sträter N. J Biol Chem 291 16477 (2016)
  12. A 37-amino acid loop in the Yarrowia lipolytica hexokinase impacts its activity and affinity and modulates gene expression. Hapeta P, Szczepańska P, Neuvéglise C, Lazar Z. Sci Rep 11 6412 (2021)
  13. Genetic and Physiological Characterization of Fructose-1,6-Bisphosphate Aldolase and Glyceraldehyde-3-Phosphate Dehydrogenase in the Crabtree-Negative Yeast Kluyveromyces lactis. Rodicio R, Schmitz HP, Heinisch JJ. Int J Mol Sci 23 772 (2022)
  14. Plasmodium vivax and human hexokinases share similar active sites but display distinct quaternary architectures. Srivastava SS, Darling JE, Suryadi J, Morris JC, Drew ME, Subramaniam S. IUCrJ 7 453-461 (2020)
  15. Crystal Structure of Kluyveromyces lactis Glucokinase (KlGlk1). Zak KM, Kalińska M, Wątor E, Kuśka K, Krutyhołowa R, Dubin G, Popowicz GM, Grudnik P. Int J Mol Sci 20 4821 (2019)
  16. Linker residues regulate the activity and stability of hexokinase 2, a promising anticancer target. Ferreira JC, Khrbtli AR, Shetler CL, Mansoor S, Ali L, Sensoy O, Rabeh WM. J Biol Chem 296 100071 (2021)
  17. Molecular mechanism of selective substrate engagement and inhibitor disengagement of cysteine synthase. Kaushik A, Rahisuddin R, Saini N, Singh RP, Kaur R, Koul S, Kumaran S. J Biol Chem 296 100041 (2021)
  18. A NMR method to determine the anomeric specificity of glucose phosphorylation. Richter T, Berger S. Bioorg Med Chem 21 2710-2714 (2013)
  19. Changing course: Glucose starvation drives nuclear accumulation of Hexokinase 2 in S. cerevisiae. Lesko MA, Chandrashekarappa DG, Jordahl EM, Oppenheimer KG, Bowman RW, Shang C, Durrant JD, Schmidt MC, O'Donnell AF. PLoS Genet 19 e1010745 (2023)
  20. Structural Analysis of Plasmodium falciparum Hexokinase Provides Novel Information about Catalysis Due to a Plasmodium-Specific Insertion. Dillenberger M, Werner AD, Velten AS, Rahlfs S, Becker K, Fritz-Wolf K. Int J Mol Sci 24 12739 (2023)
  21. Worth the Weight: Sub-Pocket EXplorer (SubPEx), a Weighted Ensemble Method to Enhance Binding-Pocket Conformational Sampling. Hellemann E, Durrant JD. J Chem Theory Comput 19 5677-5689 (2023)


Related citations provided by authors (1)

  1. Crystallization and preliminary X-ray diffraction studies of hexokinase KlHxk1 from Kluyveromyces lactis.. Kuettner EB, Kriegel TM, Keim A, Naumann M, Sträter N Acta Crystallogr Sect F Struct Biol Cryst Commun 63 430-3 (2007)

Quick links