galactokinase

Summary

Summary: An enzyme that catalyzes reversibly the formation of galactose 1-phosphate and ADP from ATP and D-galactose. Galactosamine can also act as the acceptor. A deficiency of this enzyme results in GALACTOSEMIA. EC 2.7.1.6.

Top Publications

  1. Gligoris T, Thireos G, Tzamarias D. The Tup1 corepressor directs Htz1 deposition at a specific promoter nucleosome marking the GAL1 gene for rapid activation. Mol Cell Biol. 2007;27:4198-205 pubmed
    ..We propose that Tup1 cooperates with SWR1-C and specifies Htz1 deposition at GAL1, thereby marking the promoter for rapid neutralization from its repressive effects. ..
  2. Chen M, Chen L, Zou Y, Xue M, Liang M, Jin L, et al. Wide sugar substrate specificity of galactokinase from Streptococcus pneumoniae TIGR4. Carbohydr Res. 2011;346:2421-5 pubmed publisher
    ..The galactokinase (GalKSpe4) cloned from Streptococcus pneumoniae TIGR4 had a temperature optimum of 45°C, and a pH optimum of ..
  3. Texari L, Dieppois G, Vinciguerra P, Contreras M, Groner A, Letourneau A, et al. The nuclear pore regulates GAL1 gene transcription by controlling the localization of the SUMO protease Ulp1. Mol Cell. 2013;51:807-18 pubmed publisher
    ..Altogether, our data highlight a role for the NPC-associated SUMO protease Ulp1 in regulating the sumoylation of gene-bound transcription regulators, positively affecting transcription kinetics in the context of the NPC. ..
  4. Gunde T, Tanner S, Auf der Maur A, Petrascheck M, Barberis A. Quenching accumulation of toxic galactose-1-phosphate as a system to select disruption of protein-protein interactions in vivo. Biotechniques. 2004;37:844-52 pubmed
    ..assay based on the toxicity of intracellular galactose-1-phosphate, which accumulates upon expression of a galactokinase-encoding GAL1 reporter gene in the absence of transferase activity...
  5. Ai Y, Jenkins N, Copeland N, Gilbert D, Bergsma D, Stambolian D. Mouse galactokinase: isolation, characterization, and location on chromosome 11. Genome Res. 1995;5:53-9 pubmed
    Elevated galactose levels can be caused by several enzyme defects, one of which is galactokinase. Galactokinase deficiency cause congenital cataracts during infancy and presenile cataracts in the adult population...
  6. Lemieux K, Larochelle M, Gaudreau L. Variant histone H2A.Z, but not the HMG proteins Nhp6a/b, is essential for the recruitment of Swi/Snf, Mediator, and SAGA to the yeast GAL1 UAS(G). Biochem Biophys Res Commun. 2008;369:1103-7 pubmed publisher
    ..Z, but not the HMG proteins Nhp6a/b, in promoter regions creates a specialized chromatin domain that is required for pre-initiation complex assembly at the GAL1 locus. ..
  7. Hittinger C, Carroll S. Gene duplication and the adaptive evolution of a classic genetic switch. Nature. 2007;449:677-81 pubmed
    ..use pathway includes two paralogous genes in Saccharomyces cerevisiae that encode a co-inducer (GAL3) and a galactokinase (GAL1)...
  8. Hunter M, Heyer E, Austerlitz F, Angelicheva D, Nedkova V, Briones P, et al. The P28T mutation in the GALK1 gene accounts for galactokinase deficiency in Roma (Gypsy) patients across Europe. Pediatr Res. 2002;51:602-6 pubmed
    b>Galactokinase deficiency is an inborn error of metabolism that, if untreated, results in the development of cataracts in the first weeks of life. The disorder is rare worldwide, but has a high incidence among the Roma (Gypsies)...
  9. Hawkins K, Smolke C. The regulatory roles of the galactose permease and kinase in the induction response of the GAL network in Saccharomyces cerevisiae. J Biol Chem. 2006;281:13485-92 pubmed
    ..In addition, removal of the Gal1p galactokinase from the network resulted in a regimed response due to the dual role of this enzyme in galactose catabolism ..

More Information

Publications62

  1. Hartl L, Kubicek C, Seiboth B. Induction of the gal pathway and cellulase genes involves no transcriptional inducer function of the galactokinase in Hypocrea jecorina. J Biol Chem. 2007;282:18654-9 pubmed
    The Saccharomyces cerevisiae galactokinase ScGal1, a key enzyme for D-galactose metabolism, catalyzes the conversion of D-galactose to D-galactose 1-phosphate, whereas its catalytically inactive paralogue, ScGal3, activates the ..
  2. Holden H, Thoden J, Timson D, Reece R. Galactokinase: structure, function and role in type II galactosemia. Cell Mol Life Sci. 2004;61:2471-84 pubmed
    ..b>Galactokinase catalyzes the second step in this pathway, namely the conversion of alpha- D-galactose to galactose 1-..
  3. Vaillancourt K, LeMay J, Lamoureux M, Frenette M, Moineau S, Vadeboncoeur C. Characterization of a galactokinase-positive recombinant strain of Streptococcus thermophilus. Appl Environ Microbiol. 2004;70:4596-603 pubmed
    ..This metabolic property may result from the inability of S. thermophilus to synthesize galactokinase, an enzyme of the Leloir pathway that phosphorylates intracellular galactose to generate galactose-1-phosphate...
  4. Debouck C, Riccio A, Schumperli D, McKenney K, Jeffers J, Hughes C, et al. Structure of the galactokinase gene of Escherichia coli, the last (?) gene of the gal operon. Nucleic Acids Res. 1985;13:1841-53 pubmed
    We present the nucleotide sequence of the galactokinase gene (galK) of Escherichia coli including its 5' and 3' flanking regions...
  5. Timson D, Reece R. Functional analysis of disease-causing mutations in human galactokinase. Eur J Biochem. 2003;270:1767-74 pubmed
    b>Galactokinase (EC 2.7.1.6) catalyzes the first committed step in the catabolism of galactose. The sugar is phosphorylated at position 1 at the expense of ATP...
  6. Maraini G, Hejtmancik J, Shiels A, Mackay D, Aldigeri R, Jiao X, et al. Galactokinase gene mutations and age-related cataract. Lack of association in an Italian population. Mol Vis. 2003;9:397-400 pubmed
    To investigate possible associations between sequence changes in the galactokinase gene (GALK1) and age-related cataract in a European population...
  7. Sangiuolo F, Magnani M, Stambolian D, Novelli G. Biochemical characterization of two GALK1 mutations in patients with galactokinase deficiency. Hum Mutat. 2004;23:396 pubmed
    b>Galactokinase (GALK1) deficiency is an autosomal recessive disorder, which causes cataract formation in children not maintained on a lactose-free diet. Galactokinase deficiency results from mutation in the GALK1 gene mapped on 17q24...
  8. Anders A, Lilie H, Franke K, Kapp L, Stelling J, Gilles E, et al. The galactose switch in Kluyveromyces lactis depends on nuclear competition between Gal4 and Gal1 for Gal80 binding. J Biol Chem. 2006;281:29337-48 pubmed
    ..Furthermore, we show that the KlGal80-KlGal1 interaction blocks the galactokinase activity of KlGal1 and is incompatible with KlGal80-KlGal4-AD interaction...
  9. Verhees C, Koot D, Ettema T, Dijkema C, de Vos W, van der Oost J. Biochemical adaptations of two sugar kinases from the hyperthermophilic archaeon Pyrococcus furiosus. Biochem J. 2002;366:121-7 pubmed publisher
    ..In the present study, we report the characterization of a P. furiosus galactokinase (GALK) and its comparison with the P. furiosus ADP-GLK...
  10. Hunter M, Angelicheva D, Levy H, Pueschel S, Kalaydjieva L. Novel mutations in the GALK1 gene in patients with galactokinase deficiency. Hum Mutat. 2001;17:77-8 pubmed
    b>Galactokinase deficiency is an inborn error of galactose metabolism whose major clinical manifestation is the development of cataracts during the first months of life...
  11. Kundu S, Horn P, Peterson C. SWI/SNF is required for transcriptional memory at the yeast GAL gene cluster. Genes Dev. 2007;21:997-1004 pubmed
    ..Genetic studies indicate that SWI/SNF controls transcriptional memory by antagonizing ISWI-like chromatin remodeling enzymes. ..
  12. Durairaj G, Chaurasia P, Lahudkar S, Malik S, Shukla A, Bhaumik S. Regulation of chromatin assembly/disassembly by Rtt109p, a histone H3 Lys56-specific acetyltransferase, in vivo. J Biol Chem. 2010;285:30472-9 pubmed publisher
  13. Stambolian D, Ai Y, Sidjanin D, Nesburn K, Sathe G, Rosenberg M, et al. Cloning of the galactokinase cDNA and identification of mutations in two families with cataracts. Nat Genet. 1995;10:307-12 pubmed
    b>Galactokinase is an essential enzyme for the metabolism of galactose and its deficiency causes congenital cataracts during infancy and presenile cataracts in the adult population...
  14. Meyer J, Walker Jonah A, Hollenberg C. Galactokinase encoded by GAL1 is a bifunctional protein required for induction of the GAL genes in Kluyveromyces lactis and is able to suppress the gal3 phenotype in Saccharomyces cerevisiae. Mol Cell Biol. 1991;11:5454-61 pubmed
    ..The data show that the K. lactis GAL1 gene product has, in addition to galactokinase activity, a function required for induction of the lactose system...
  15. Conant G, Wolfe K. Turning a hobby into a job: how duplicated genes find new functions. Nat Rev Genet. 2008;9:938-50 pubmed publisher
    ..Interestingly, in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication. ..
  16. Hittinger C, Rokas A, Carroll S. Parallel inactivation of multiple GAL pathway genes and ecological diversification in yeasts. Proc Natl Acad Sci U S A. 2004;101:14144-9 pubmed
    ..Inactivated genes may generally serve as markers of specific functions made dispensable by recent adaptive shifts. ..
  17. Tang M, Wierenga K, Elsas L, Lai K. Molecular and biochemical characterization of human galactokinase and its small molecule inhibitors. Chem Biol Interact. 2010;188:376-85 pubmed publisher
    Human galactokinase (GALK) is the first enzyme in the Leloir pathway, converting ?-d-galactose into galactose-1-phosphate (Gal-1-P)...
  18. Bergsma D, Ai Y, Skach W, Nesburn K, Anoia E, Van Horn S, et al. Fine structure of the human galactokinase GALK1 gene. Genome Res. 1996;6:980-5 pubmed
    Defects in the human GALK1 gene result in galactokinase deficiency and cataract formation. We have isolated this gene and established its structural organization. The gene contains 8 exons and spans approximately 7.3 kb of genomic DNA...
  19. Asada M, Okano Y, Imamura T, Suyama I, Hase Y, Isshiki G. Molecular characterization of galactokinase deficiency in Japanese patients. J Hum Genet. 1999;44:377-82 pubmed
    b>Galactokinase (GALK) deficiency is an autosomal recessive disorder, which causes cataract formation in children not maintained on a lactose-free diet...
  20. Zacharioudakis I, Gligoris T, Tzamarias D. A yeast catabolic enzyme controls transcriptional memory. Curr Biol. 2007;17:2041-6 pubmed
    ..Instead, the important memory determinant is a close Gal3 homolog, the highly expressed Gal1 galactokinase, the residual activity of which preserves memory in progeny cells by rapidly turning on the Gal4 activator ..
  21. Byrum S, Raman A, Taverna S, Tackett A. ChAP-MS: a method for identification of proteins and histone posttranslational modifications at a single genomic locus. Cell Rep. 2012;2:198-205 pubmed publisher
    ..ChAP-MS should yield insight into the regulatory mechanisms of transcription and help identify factors that epigenetically control chromatin function. ..
  22. Kolosha V, Anoia E, de Cespedes C, Gitzelmann R, Shih L, Casco T, et al. Novel mutations in 13 probands with galactokinase deficiency. Hum Mutat. 2000;15:447-53 pubmed
    b>Galactokinase is an essential enzyme in the metabolism of galactose. Patients with deficiencies in galactokinase exhibit early-onset cataracts...
  23. Timson D, Reece R. Kinetic analysis of yeast galactokinase: implications for transcriptional activation of the GAL genes. Biochimie. 2002;84:265-72 pubmed
    b>Galactokinase (EC 2.7.1.6) catalyses the first step in the catabolism of galactose. Yeast galactokinase, Gal1p, and the closely related but catalytically inactive Gal3p, also function as ligand sensors in the GAL genetic switch...
  24. Larschan E, Winston F. The Saccharomyces cerevisiae Srb8-Srb11 complex functions with the SAGA complex during Gal4-activated transcription. Mol Cell Biol. 2005;25:114-23 pubmed
    ..Finally, Srb9 association also requires TBP. These results suggest that Srb8-Srb11 associates with the GAL1 promoter subsequent to SAGA binding, and that the binding of TBP and Srb8-Srb11 is interdependent. ..
  25. Okano Y, Asada M, Fujimoto A, Ohtake A, Murayama K, Hsiao K, et al. A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, "Osaka," in Asians. Am J Hum Genet. 2001;68:1036-42 pubmed
    b>Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized by hypergalactosemia and cataract formation...
  26. Maya D, Quintero M, de la Cruz Muñoz Centeno M, Chávez S. Systems for applied gene control in Saccharomyces cerevisiae. Biotechnol Lett. 2008;30:979-87 pubmed publisher
    ..We examine here new expression systems that have been described, including improvements of classical ones and new strategies of artificial gene control that have been applied in functional genomics. ..
  27. Kaplan C, Tugal H, Baker A. Isolation of a cDNA encoding an Arabidopsis galactokinase by functional expression in yeast. Plant Mol Biol. 1997;34:497-506 pubmed
    A cDNA clone encoding Arabidopsis thaliana galactokinase was fortuitously isolated during the course of a screen for plant homologues of a Saccharomyces cerevisiae peroxisome assembly gene, PAS9...
  28. Sellick C, Reece R. Contribution of amino acid side chains to sugar binding specificity in a galactokinase, Gal1p, and a transcriptional inducer, Gal3p. J Biol Chem. 2006;281:17150-5 pubmed
    The crystal structure of the yeast galactokinase, Gal1p, in the presence of its substrates has been solved recently...
  29. Frey P. The Leloir pathway: a mechanistic imperative for three enzymes to change the stereochemical configuration of a single carbon in galactose. FASEB J. 1996;10:461-70 pubmed
    ..of galactose and glucose takes place only by way of the Leloir pathway and requires the three enzymes galactokinase, galactose-1-P uridylyltransferase, and UDP-galactose 4-epimerase...
  30. McIsaac R, Silverman S, McClean M, Gibney P, Macinskas J, Hickman M, et al. Fast-acting and nearly gratuitous induction of gene expression and protein depletion in Saccharomyces cerevisiae. Mol Biol Cell. 2011;22:4447-59 pubmed publisher
    ..With galactokinase Gal1p and transcriptional activator Gal4p absent, the system is fast-acting, resulting in readily detectable ..
  31. Kim M, Lee T, Lim H, Seo J. Production of antithrombotic hirudin in GAL1-disrupted Saccharomyces cerevisiae. Appl Microbiol Biotechnol. 2004;65:259-62 pubmed
    A gratuitous strain was developed by disrupting the GAL1 gene (galactokinase) of recombinant Saccharomyces cerevisiae harboring the antithrombotic hirudin gene in the chromosome under the control of the GAL10 promoter...
  32. Timson D, Reece R. Sugar recognition by human galactokinase. BMC Biochem. 2003;4:16 pubmed
    b>Galactokinase catalyses the first committed step of galactose catabolism in which the sugar is phosphorylated at the expense of MgATP...
  33. Seiboth B, Hartl L, Pail M, Fekete E, Karaffa L, Kubicek C. The galactokinase of Hypocrea jecorina is essential for cellulase induction by lactose but dispensable for growth on d-galactose. Mol Microbiol. 2004;51:1015-25 pubmed
    ..of lactose metabolism and its role in cellulase formation, we have cloned and characterized the gal1 (galactokinase) gene of H. jecorina, which catalyses the first step in d-galactose catabolism...
  34. Vodala S, Abruzzi K, Rosbash M. The nuclear exosome and adenylation regulate posttranscriptional tethering of yeast GAL genes to the nuclear periphery. Mol Cell. 2008;31:104-13 pubmed publisher
    ..We propose that this dot RNA, probably via RNP proteins, contributes to the physical tether linking the GAL1 gene to the nuclear periphery. ..
  35. Bork P, Sander C, Valencia A. Convergent evolution of similar enzymatic function on different protein folds: the hexokinase, ribokinase, and galactokinase families of sugar kinases. Protein Sci. 1993;2:31-40 pubmed
    ..The flexible combination of active sites and three-dimensional folds observed in nature can be exploited by protein engineers in designing and optimizing enzymatic function. ..
  36. Wierenga K, Lai K, Buchwald P, Tang M. High-throughput screening for human galactokinase inhibitors. J Biomol Screen. 2008;13:415-23 pubmed publisher
    ..Several lines of evidence indicate that an elevated level of galactose-1-phosphate (gal-1-p), the product of galactokinase (GALK), is a major, if not sole, pathogenic mechanism in patients with classic galactosemia...
  37. Yang F, Agulian T, Sudati J, Rhoads D, Levitsky L. Developmental regulation of galactokinase in suckling mouse liver by the Egr-1 transcription factor. Pediatr Res. 2004;55:822-9 pubmed
    ..In screening the sequences of the genes involved in lactose assimilation, we found that the galactokinase gene Glk contains four potential Egr-1 binding sites in its proximal promoter...
  38. Pokholok D, Hannett N, Young R. Exchange of RNA polymerase II initiation and elongation factors during gene expression in vivo. Mol Cell. 2002;9:799-809 pubmed
    ..These results suggest a revised model for transcription initiation and elongation apparatuses in living cells. ..
  39. Bosch A, Bakker H, Van Gennip A, van Kempen J, Wanders R, Wijburg F. Clinical features of galactokinase deficiency: a review of the literature. J Inherit Metab Dis. 2002;25:629-34 pubmed
    b>Galactokinase deficiency (McKusick 230200) is a rare autosomal recessive inborn error of galactose metabolism...
  40. Thoden J, Holden H. Molecular structure of galactokinase. J Biol Chem. 2003;278:33305-11 pubmed publisher
    b>Galactokinase plays a key role in normal galactose metabolism by catalyzing the ATP-dependent phosphorylation of alpha-D-galactose to galactose 1-phosphate...
  41. Megarity C, Huang M, Warnock C, Timson D. The role of the active site residues in human galactokinase: implications for the mechanisms of GHMP kinases. Bioorg Chem. 2011;39:120-6 pubmed publisher
    b>Galactokinase catalyses the phosphorylation of galactose at the expense of ATP...
  42. Green E, Jiang Y, Joyner R, Weis K. A negative feedback loop at the nuclear periphery regulates GAL gene expression. Mol Biol Cell. 2012;23:1367-75 pubmed publisher
  43. Jojart B, Szori M, Izsak R, Marsi I, Laszlo A, Csizmadia I, et al. The effect of a Pro²?Thr point mutation on the local structure and stability of human galactokinase enzyme-a theoretical study. J Mol Model. 2011;17:2639-49 pubmed publisher
    b>Galactokinase is responsible for the phosphorylation of ?-D: -galactose, which is an important step in the metabolism of the latter...
  44. Kar R, Qureshi M, Dasadhikari A, Zahir T, Venkatesh K, Bhat P. Stochastic galactokinase expression underlies GAL gene induction in a GAL3 mutant of Saccharomyces cerevisiae. FEBS J. 2014;281:1798-817 pubmed publisher
    ..We suggest that the asymmetric expression pattern between GAL1 and GAL3 results in the ability of S. cerevisiae to activate the GAL pathway by conferring nongenetic heterogeneity...
  45. Park H, Kim Y, Park K, Kim J, Song Y, Song J. A novel c.-22T>C mutation in GALK1 promoter is associated with elevated galactokinase phenotype. BMC Med Genet. 2009;10:29 pubmed publisher
    Many genetic variations of GALK1 have been identified in the patients with galactokinase (GALK1) deficiency. However, the molecular characteristics of GALK1 in individuals with elevated GALK1 activity are relatively unknown...
  46. Park H, Bang Y, Park K, Kim J, Jeong B, Kim Y, et al. Molecular and biochemical characterization of the GALK1 gene in Korean patients with galactokinase deficiency. Mol Genet Metab. 2007;91:234-8 pubmed
    b>Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized by elevation of blood galactose concentration and diminished galactose-1-phosphate, leading to the production of galactitol...
  47. Thoden J, Sellick C, Timson D, Reece R, Holden H. Molecular structure of Saccharomyces cerevisiae Gal1p, a bifunctional galactokinase and transcriptional inducer. J Biol Chem. 2005;280:36905-11 pubmed
    ..Understanding the manner in which two of the proteins that function in transcriptional regulation interact with one another is an important step in determining the overall molecular mechanism of this switch. ..
  48. Yang J, Fu X, Jia Q, Shen J, Biggins J, Jiang J, et al. Studies on the substrate specificity of Escherichia coli galactokinase. Org Lett. 2003;5:2223-6 pubmed
    ..This work focuses upon the development of a high-throughput colorimetric galactokinase (GalK) assay and its application toward probing the substrate specificity and kinetic parameters of ..
  49. Kalaydjieva L, Perez Lezaun A, Angelicheva D, Onengut S, Dye D, Bosshard N, et al. A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am J Hum Genet. 1999;65:1299-307 pubmed
    b>Galactokinase deficiency is an inborn error in the first step of galactose metabolism. Its major clinical manifestation is the development of cataracts in the first weeks of life...
  50. Egert A, Peters S, Guyot C, Stieger B, Keller F. An Arabidopsis T-DNA insertion mutant for galactokinase (AtGALK, At3g06580) hyperaccumulates free galactose and is insensitive to exogenous galactose. Plant Cell Physiol. 2012;53:921-9 pubmed publisher
    b>Galactokinase (GALK, EC 2.7.1.6) is a cytosolic enzyme with a wide occurrence across the taxonomic kingdoms. It catalyzes the phosphorylation of ?-d-galactose (Gal) to ?-d-Gal-1-P...
  51. Sherson S, Gy I, Medd J, Schmidt R, Dean C, Kreis M, et al. The arabinose kinase, ARA1, gene of Arabidopsis is a novel member of the galactose kinase gene family. Plant Mol Biol. 1999;39:1003-12 pubmed
    ..Both GAL1 and ARA1 cross-hybridise at low stringency to other sequences suggesting the presence of additional members of the galactose kinase gene family. ..
  52. Shin Buehring Y, Stuempfig L, Pouget E, Rahm P, Schaub J. Characterization of galactose-1-phosphate uridyl-transferase and galactokinase in human organs from the fetus and adult. Clin Chim Acta. 1981;112:257-65 pubmed
    Some properties of galactose-1-phosphate uridyltransferase (EC 2.7.7.12) and galactokinase (EC 2.7.1.6) were investigated in human organs, i.e...
  53. Menzel R, Gellert M. Fusions of the Escherichia coli gyrA and gyrB control regions to the galactokinase gene are inducible by coumermycin treatment. J Bacteriol. 1987;169:1272-8 pubmed
    ..In this paper we describe fusions of both the gyrA and gyrB 5' sequences to the E. coli galactokinase gene...