udpglucose 4 epimerase

Summary

Summary: A necessary enzyme in the metabolism of galactose. It reversibly catalyzes the conversion of UDPglucose to UDPgalactose. NAD+ is an essential component for enzymatic activity. EC 5.1.3.2.

Top Publications

  1. Shaw M, Bond C, Roper J, Gourley D, Ferguson M, Hunter W. High-resolution crystal structure of Trypanosoma brucei UDP-galactose 4'-epimerase: a potential target for structure-based development of novel trypanocides. Mol Biochem Parasitol. 2003;126:173-80 pubmed
    ..brucei enzyme. Such a significant difference could be exploited by the structure-based design of selective inhibitors using the structure of the trypanosomatid enzyme as a template. ..
  2. Thoden J, Hegeman A, Wesenberg G, Chapeau M, Frey P, Holden H. Structural analysis of UDP-sugar binding to UDP-galactose 4-epimerase from Escherichia coli. Biochemistry. 1997;36:6294-304 pubmed
    ..24 A. The only significant differences between the various enzyme/UDP-sugar models occur in two of the dihedral angles defining the conformation of the UDP-sugar ligands. ..
  3. Urbaniak M, Tabudravu J, Msaki A, Matera K, Brenk R, Jaspars M, et al. Identification of novel inhibitors of UDP-Glc 4'-epimerase, a validated drug target for african sleeping sickness. Bioorg Med Chem Lett. 2006;16:5744-7 pubmed
    ..The inhibitors possess low micromolar potency against the T. brucei and human enzymes in vitro, display a degree of selectivity between the two enzymes, and are cytotoxic to cultured T. brucei and mammalian cells...
  4. Holden H, Rayment I, Thoden J. Structure and function of enzymes of the Leloir pathway for galactose metabolism. J Biol Chem. 2003;278:43885-8 pubmed
  5. Brahma A, Banerjee N, Bhattacharyya D. UDP-galactose 4-epimerase from Kluyveromyces fragilis--catalytic sites of the homodimeric enzyme are functional and regulated. FEBS J. 2009;276:6725-40 pubmed publisher
  6. Roper J, Guther M, Macrae J, Prescott A, Hallyburton I, Acosta Serrano A, et al. The suppression of galactose metabolism in procylic form Trypanosoma brucei causes cessation of cell growth and alters procyclin glycoprotein structure and copy number. J Biol Chem. 2005;280:19728-36 pubmed
    ..The parasites compensated, ultimately unsuccessfully, by expressing 10-fold more procyclin. The implications of these data with respect to the relative roles of procyclin polypeptide and carbohydrate are discussed...
  7. Roper J, Guther M, Milne K, Ferguson M. Galactose metabolism is essential for the African sleeping sickness parasite Trypanosoma brucei. Proc Natl Acad Sci U S A. 2002;99:5884-9 pubmed
    ..The results show that enzymes and transporters involved in galactose metabolism may be considered as potential therapeutic targets against African trypanosomiasis. ..
  8. Bahat Samet E, Castro Sowinski S, Okon Y. Arabinose content of extracellular polysaccharide plays a role in cell aggregation of Azospirillum brasilense. FEMS Microbiol Lett. 2004;237:195-203 pubmed
    ..Thus, aggregation could constitute a protected model of growth that allows survival in a hostile environment. The occurrence of exoC and rmlD was detected in several species of Azospirillum...
  9. Torkkell S, Ylihonko K, Hakala J, Skurnik M, Mantsala P. Characterization of Streptomyces nogalater genes encoding enzymes involved in glycosylation steps in nogalamycin biosynthesis. Mol Gen Genet. 1997;256:203-9 pubmed
    ..Interestingly, SnoA, a transcriptional activator for the sno minimal polyketide synthase, is also needed to express this cluster. ..

More Information

Publications62

  1. Wohlers T, Fridovich Keil J. Studies of the V94M-substituted human UDPgalactose-4-epimerase enzyme associated with generalized epimerase-deficiency galactosaemia. J Inherit Metab Dis. 2000;23:713-29 pubmed
  2. Canals R, Jimenez N, Vilches S, Regue M, Merino S, Tomas J. Role of Gne and GalE in the virulence of Aeromonas hydrophila serotype O34. J Bacteriol. 2007;189:540-50 pubmed
    ..hydrophila mutant strains or the complemented mutants, allowed us to confirm a clear relationship between the virulence of these strains and the presence/absence of the O34 antigen LPS. ..
  3. Brahma A, Bhattacharyya D. UDP-galactose 4-epimerase from Kluyveromyces fragilis. Evidence for independent mutarotation site. Eur J Biochem. 2004;271:58-68 pubmed
    ..In addition to the inducible bifunctional epimerase/mutarotase, K. fragilis contained a smaller constitutive monomeric mutarotase of approximately 35 kDa. ..
  4. Schulz J, Ross K, Malmstrom K, Krieger M, Fridovich Keil J. Mediators of galactose sensitivity in UDP-galactose 4'-epimerase-impaired mammalian cells. J Biol Chem. 2005;280:13493-502 pubmed
    ..These data offer important insights into the mechanism of galactose sensitivity in epimerase-impaired cells and suggest a potential novel therapy for patients with epimerase-deficiency galactosemia...
  5. Boels I, Ramos A, Kleerebezem M, de Vos W. Functional analysis of the Lactococcus lactis galU and galE genes and their impact on sugar nucleotide and exopolysaccharide biosynthesis. Appl Environ Microbiol. 2001;67:3033-40 pubmed publisher
    ..Addition of galactose restored wild-type growth in the galE disruption mutant, while the level of EPS production was approximately one-half the wild-type level...
  6. Thoden J, Wohlers T, Fridovich Keil J, Holden H. Molecular basis for severe epimerase deficiency galactosemia. X-ray structure of the human V94m-substituted UDP-galactose 4-epimerase. J Biol Chem. 2001;276:20617-23 pubmed
    ..The net effect of the V94M substitution is an opening up of the Ala(93) to Glu(96) surface loop, which allows free rotation of the sugars into nonproductive binding modes. ..
  7. Blixt O, Brown J, Schur M, Wakarchuk W, Paulson J. Efficient preparation of natural and synthetic galactosides with a recombinant beta-1,4-galactosyltransferase-/UDP-4'-gal epimerase fusion protein. J Org Chem. 2001;66:2442-8 pubmed
    ..Thus, bacterially expressed fusion protein is well suited for the facile and economic preparation of natural oligosaccharides and synthetic derivatives based on the lactosamine core. ..
  8. Wubben M, Rodermel S, Baum T. Mutation of a UDP-glucose-4-epimerase alters nematode susceptibility and ethylene responses in Arabidopsis roots. Plant J. 2004;40:712-24 pubmed
    ..We conclude that RHD1 is a likely target of root-specific negative regulation by ethylene and that loss of RHD1 function results in a heightened sensitivity of root tissues to both ethylene and auxin. ..
  9. Bandyopadhyay S, Chakrabarti J, Banerjee S, Pal A, Bhattacharyya D, Goswami S, et al. Prenatal exposure to high galactose adversely affects initial gonadal pool of germ cells in rats. Hum Reprod. 2003;18:276-82 pubmed
    ..We investigated if development of POF under experimental galactosaemia-like conditions was attributed to impaired germ cell migration...
  10. Mori T, Suenaga H, Miyazaki K. A metagenomic approach to the identification of UDP-glucose 4-epimerase as a menadione resistance protein. Biosci Biotechnol Biochem. 2008;72:1611-4 pubmed
    ..Because UGE is involved in the biosynthesis of lipopolysaccharides, it may have contributed to forming a permeability barrier against lipophilic quinones. ..
  11. Petry K, Reichardt J. The fundamental importance of human galactose metabolism: lessons from genetics and biochemistry. Trends Genet. 1998;14:98-102 pubmed
  12. Shao J, Hayashi T, Wang P. Enhanced production of alpha-galactosyl epitopes by metabolically engineered Pichia pastoris. Appl Environ Microbiol. 2003;69:5238-42 pubmed
    ..The Pichia system described here is simple and flexible. This work demonstrates that recombinant P. pastoris is an excellent alternative to Escherichia coli transformants in large-scale synthesis of oligosaccharides. ..
  13. Petrovska L, Hewinson R, Dougan G, Maskell D, Woodward M. Brucella melitensis 16M: characterisation of the galE gene and mouse immunisation studies with a galE deficient mutant. Vet Microbiol. 1999;65:21-36 pubmed
    ..CD-1 mice immunised with B. melitensis 16M galE were protected against B. melitensis 16M challenge. ..
  14. Guo H, Yi W, Li L, Wang P. Three UDP-hexose 4-epimerases with overlapping substrate specificity coexist in E. coli O86:B7. Biochem Biophys Res Commun. 2007;356:604-9 pubmed
    ..These findings provide new clues for understanding the mechanism of O-antigen biosynthesis. ..
  15. Thoden J, Frey P, Holden H. High-resolution X-ray structure of UDP-galactose 4-epimerase complexed with UDP-phenol. Protein Sci. 1996;5:2149-61 pubmed
  16. Daenzer J, Fridovich Keil J. Drosophila melanogaster Models of Galactosemia. Curr Top Dev Biol. 2017;121:377-395 pubmed publisher
    ..Drosophila melanogaster provides a genetically and biochemically facile model for these conditions, enabling studies that address mechanism and open the door for novel approaches to intervention. ..
  17. Openo K, Schulz J, Vargas C, Orton C, Epstein M, Schnur R, et al. Epimerase-deficiency galactosemia is not a binary condition. Am J Hum Genet. 2006;78:89-102 pubmed
    ..Long-term follow-up studies of these and other patients will be required to elucidate the clinical significance of these biochemical abnormalities and the potential impact of dietary intervention on outcome. ..
  18. Brahma A, Bhattacharyya D. UDP-galactose 4-epimerase from Kluyveromyces fragilis: existence of subunit independent functional site. FEBS Lett. 2004;577:27-34 pubmed
    ..Specific modification reagents further confirmed that the cysteine residues required for catalysis and coenzyme fluorophore reside exclusively on a single subunit negating a 'subunit sharing model' of its catalytic site. ..
  19. Shin S, Choi J, di Luccio E, Lee Y, Lee S, Lee S, et al. The structural basis of substrate promiscuity in UDP-hexose 4-epimerase from the hyperthermophilic Eubacterium Thermotoga maritima. Arch Biochem Biophys. 2015;585:39-51 pubmed publisher
    ..coli GalE, supports the notion that TMGalE might exhibit the earliest form of sugar-epimerizing enzymes in the evolution of galactose metabolism. ..
  20. Zhu H, Sun B, Li Y, Meng D, Zheng S, Wang T, et al. KfoA, the UDP-glucose-4-epimerase of Escherichia coli strain O5:K4:H4, shows preference for acetylated substrates. Appl Microbiol Biotechnol. 2018;102:751-761 pubmed publisher
    ..Our results deepen the understanding of the mechanism of KfoA and will assist in the research into the metabolic engineering for chondroitin sulfate production. ..
  21. Jumbo Lucioni P, PARKINSON W, Kopke D, Broadie K. Coordinated movement, neuromuscular synaptogenesis and trans-synaptic signaling defects in Drosophila galactosemia models. Hum Mol Genet. 2016;25:3699-3714 pubmed publisher
  22. Bang Y, Nguyen T, Trinh T, Kim Y, Song J, Song Y. Functional analysis of mutations in UDP-galactose-4-epimerase (GALE) associated with galactosemia in Korean patients using mammalian GALE-null cells. FEBS J. 2009;276:1952-61 pubmed publisher
    ..Our observations show that altered protein stability is due to misfolding and that loss or reduction of enzyme activity is responsible for the molecular defects underlying GALE-deficiency galactosemia...
  23. Suzuki O, Tasaki K, Kusakabe T, Abe M. UDP-GlcNAc2-epimerase regulates cell surface sialylation and ceramide-induced cell death in human malignant lymphoma. Int J Mol Med. 2008;22:339-48 pubmed
    ..In conclusion, in human malignant lymphoma, ceramide and its metabolite-induced cell death is regulated by the amount of sialic acid on the cell surface which in turn is regulated by mRNA expression of UDP-GlcNAc2-epimerase. ..
  24. Santhanagopalan V, Coker C, Radulovic S. Characterization of RP 333, a gene encoding CapD of Rickettsia prowazekii with UDP-glucose 4-epimerase activity. Gene. 2006;369:119-25 pubmed publisher
    ..prowazekii vaccine, generation of new antibiotics, and opening the way for research in membrane biogenesis with respect to the parasitic lifestyle of Rickettsia...
  25. Maceratesi P, Daude N, Dallapiccola B, Novelli G, Allen R, Okano Y, et al. Human UDP-galactose 4' epimerase (GALE) gene and identification of five missense mutations in patients with epimerase-deficiency galactosemia. Mol Genet Metab. 1998;63:26-30 pubmed
    ..These results confirm that epimerase-deficiency galactosemia is the result of missense mutations in the GALE gene and indicate that the disease is characterized by extensive allelic heterogeneity...
  26. Henderson M, Holton J, MacFaul R. Further observations in a case of uridine diphosphate galactose-4-epimerase deficiency with a severe clinical presentation. J Inherit Metab Dis. 1983;6:17-20 pubmed
    ..The significance of the observation is discussed with respect to the pathogenesis and treatment of the disease. ..
  27. Remy E, Meyer M, Blaise F, Simon U, Kuhn D, Balesdent M, et al. A key enzyme of the Leloir pathway is involved in pathogenicity of Leptosphaeria maculans toward oilseed rape. Mol Plant Microbe Interact. 2009;22:725-36 pubmed publisher
    ..maculans. This finding, along with similar data obtained from the related species Stagonospora nodorum, indicates the importance of in planta nutrition for the success of infection of plants by fungi belonging to class Dothideomycete. ..
  28. Fry B, Korolik V, ten Brinke J, Pennings M, Zalm R, Teunis B, et al. The lipopolysaccharide biosynthesis locus of Campylobacter jejuni 81116. Microbiology. 1998;144 ( Pt 8):2049-61 pubmed
    ..They consisted of three homologues of sugar biosynthesis genes, two homologues of transport genes and six homologues of sugar transferases...
  29. Kazimierczak K, Scott K, Kelly D, Aminov R. Tetracycline resistome of the organic pig gut. Appl Environ Microbiol. 2009;75:1717-22 pubmed publisher
  30. Dormann P, Benning C. Functional expression of uridine 5'-diphospho-glucose 4-epimerase (EC 5.1.3.2) from Arabidopsis thaliana in Saccharomyces cerevisiae and Escherichia coli. Arch Biochem Biophys. 1996;327:27-34 pubmed
    ..Its availability provides the means to investigate the role of UDP-glucose epimerase for the biosynthesis of UDP-galactose as precursor of galactolipids and cell wall polysaccharides. ..
  31. Lee F, Stephens D, Gibson B, Engstrom J, Zhou D, Apicella M. Microheterogeneity of Neisseria lipooligosaccharide: analysis of a UDP-glucose 4-epimerase mutant of Neisseria meningitidis NMB. Infect Immun. 1995;63:2508-15 pubmed
    ..These data suggest that NMB has a glycosyltransferase capable of polymerizing glucose moieties as an alternative biosynthetic pathway to the wild-type lacto-N-neotetrose structure. ..
  32. Degeest B, Mozzi F, De Vuyst L. Effect of medium composition and temperature and pH changes on exopolysaccharide yields and stability during Streptococcus thermophilus LY03 fermentations. Int J Food Microbiol. 2002;79:161-74 pubmed
    ..These results contribute to a better understanding of the physiological and chemical factors influencing EPS production and degradation. ..
  33. Timson D. Functional analysis of disease-causing mutations in human UDP-galactose 4-epimerase. FEBS J. 2005;272:6170-7 pubmed
    ..Furthermore, there is an approximate correlation between the severity of these defects in the protein structure and function, and the symptoms observed in patients...
  34. Macrae J, Obado S, Turnock D, Roper J, Kierans M, Kelly J, et al. The suppression of galactose metabolism in Trypanosoma cruzi epimastigotes causes changes in cell surface molecular architecture and cell morphology. Mol Biochem Parasitol. 2006;147:126-36 pubmed
    ..The apparent haploid deficiency suggests that epimerase levels are close to limiting, at least in the epimastigote form, and might be exploited as a potential drug target. ..
  35. Fukasawa T, Segawa T, Nogi Y. Uridine diphosphate glucose-4-epimerase and galactose-1-phosphate uridylyltransferase from Saccharomyces cerevisiae. Methods Enzymol. 1982;89 Pt D:584-92 pubmed
  36. Alano A, Almashanu S, Chinsky J, Costeas P, Blitzer M, Wulfsberg E, et al. Molecular characterization of a unique patient with epimerase-deficiency galactosaemia. J Inherit Metab Dis. 1998;21:341-50 pubmed
  37. Jennings M, van der Ley P, Wilks K, Maskell D, Poolman J, Moxon E. Cloning and molecular analysis of the galE gene of Neisseria meningitidis and its role in lipopolysaccharide biosynthesis. Mol Microbiol. 1993;10:361-9 pubmed
    ..These results are consistent with an essential role for galE in the incorporation of galactose into meningococcal lipopolysaccharide...
  38. Louie G, Baiga T, Bowman M, Koeduka T, Taylor J, Spassova S, et al. Structure and reaction mechanism of basil eugenol synthase. PLoS ONE. 2007;2:e993 pubmed
  39. Miyazawa S. Protein sequence-structure alignment based on site-alignment probabilities. Genome Inform Ser Workshop Genome Inform. 2000;11:141-50 pubmed
    ..Remarkably, by this method some individual sequence-structure pairs are detected having only 5-20% sequence identity. ..
  40. Nayar S, Bhattacharyya D. UDP-galactose 4-epimerase from Escherichia coli: equilibrium unfolding studies. Indian J Biochem Biophys. 2001;38:353-60 pubmed
    ..Thermodynamical parameters associated with some transitions have been quantitated. The results have been discussed with the X-ray crystallographic structure of the enzyme. ..
  41. Nawaz M, Wang R, Khan S, Khan A. Detection of galE gene by polymerase chain reaction in campylobacters associated with Guillain-Barre syndrome. Mol Cell Probes. 2003;17:313-7 pubmed
    ..E. coli and Salmonella spp. The entire diagnostic assay, including template preparation, amplification and electrophoresis, can be completed within 6 h. ..
  42. Majumdar S, Ghatak J, Mukherji S, Bhattacharjee H, Bhaduri A. UDPgalactose 4-epimerase from Saccharomyces cerevisiae. A bifunctional enzyme with aldose 1-epimerase activity. Eur J Biochem. 2004;271:753-9 pubmed
    ..cerevisiae UDPgalactose 4-epimerase is a bifunctional enzyme with aldose 1-epimerase activity. The active sites for these two enzymatic activities are located in different regions of the epimerase holoenzyme. ..
  43. Virji M, Stimson E, Makepeace K, Dell A, Morris H, Payne G, et al. Posttranslational modifications of meningococcal pili. Identification of a common trisaccharide substitution on variant pilins of strain C311. Ann N Y Acad Sci. 1996;797:53-64 pubmed
    ..We have identified a completely novel protein/carbohydrate linkage on a multimeric protein that is an essential virulence determinant in N. meningitidis. ..
  44. Zhang T, Wang L, Jiang R, Li Y. [Cloning and expression of UDP-glucose-4-epimerase gene from Streptomyces and characteristics of the enzyme]. Wei Sheng Wu Xue Bao. 2005;45:881-4 pubmed
    ..The above research lays a very good foundation for study on functions of the ste 19 gene in Ebosin biosynthesis. ..
  45. Moyrand F, Lafontaine I, Fontaine T, Janbon G. UGE1 and UGE2 regulate the UDP-glucose/UDP-galactose equilibrium in Cryptococcus neoformans. Eukaryot Cell. 2008;7:2069-77 pubmed publisher
  46. Stammers D, Ren J, Leslie K, Nichols C, Lamb H, Cocklin S, et al. The structure of the negative transcriptional regulator NmrA reveals a structural superfamily which includes the short-chain dehydrogenase/reductases. EMBO J. 2001;20:6619-26 pubmed
    ..The SDR fold appears to have been adapted for other roles including non-enzymatic control functions such as transcriptional regulation and is likely to be more widespread than previously recognized. ..
  47. Nishimura Y, Tajima G, Dwi Bahagia A, Sakamoto A, Ono H, Sakura N, et al. Differential diagnosis of neonatal mild hypergalactosaemia detected by mass screening: clinical significance of portal vein imaging. J Inherit Metab Dis. 2004;27:11-8 pubmed
    ..Additionally, determination of total bile acids and alpha-fetoprotein is helpful in identifying the aetiology of hypergalactosaemia in infants. ..
  48. Brinkmann N, Malissard M, Ramuz M, Romer U, Schumacher T, Berger E, et al. Chemo-enzymatic synthesis of the Galili epitope Gal(alpha)(1-->3)Galbeta(1-->4)GlcNAc on a homogeneously soluble PEG polymer by a multi-enzyme system. Bioorg Med Chem Lett. 2001;11:2503-6 pubmed
    ..Thus the advantages of classic chemistry/enzymology and solid-phase synthesis could be united in one. Subsequent hydrogenolytic cleavage afforded the free alpha-Gal trisaccharide. ..
  49. Thoden J, Frey P, Holden H. Molecular structure of the NADH/UDP-glucose abortive complex of UDP-galactose 4-epimerase from Escherichia coli: implications for the catalytic mechanism. Biochemistry. 1996;35:5137-44 pubmed
    ..Furthermore, the abortive complex model described here suggests that Ser 124 and Tyr 149 are likely to play important roles in the catalytic mechanism of the enzyme. ..
  50. Trisler P, Gottesman S. lon transcriptional regulation of genes necessary for capsular polysaccharide synthesis in Escherichia coli K-12. J Bacteriol. 1984;160:184-91 pubmed
    ..Therefore, the regulatory system described here does not extend to all genes in the colanic acid synthesis pathway. ..
  51. Henderson J, Huguenin S, Cowan T, Fridovich Keil J. A PCR-based method for detecting known mutations in the human UDP galactose-4'-epimerase gene associated with epimerase-deficiency galactosemia. Clin Genet. 2001;60:350-5 pubmed
  52. Koropatkin N, Liu H, Holden H. High resolution x-ray structure of tyvelose epimerase from Salmonella typhi. J Biol Chem. 2003;278:20874-81 pubmed
    ..On the basis of the observed binding mode for CDP, it is possible to predict the manner in which the substrate, CDP-paratose, and the product, CDP-tyvelose, might be accommodated within the active site of tyvelose epimerase. ..
  53. Bharatan S, Reddy M, Gowrishankar J. Distinct signatures for mutator sensitivity of lacZ reversions and for the spectrum of lacI/lacO forward mutations on the chromosome of nondividing Escherichia coli. Genetics. 2004;166:681-92 pubmed