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Bioactive Conformation I pp 217–257Cite as

Glycosyltransferase Structure and Function

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Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 272))

Abstract

The biosynthesis of the oligosaccharides and polysaccharides observed in any organism requires the existence of a repertoire of glycosyltransferase enzymes that catalyze the sequential transfer of sugars from a specific activated donor to a specific acceptor molecule to form regio- and stereospecific glycosidic linkages. A viral genome may encode just one glycosyltransferase, while a mammalian genome encodes hundreds of these enzymes. It is notable that approximately 1% of open reading frames over all sequenced genomes have been found to be glycosyltransferases, which is a fraction comparable to that allotted to kinases. Glycosyltransferases are a highly diverse group of enzymes with little homology even among enzymes that share the same substrate specificity. Classification of glycosyltransferases according to sequence homology reveals at least 86 families; however, to date only 27 of these families have members with known structure. This is in sharp contrast with glycosylhydrolases, which to date have published structures for 70 of the so far described 102 classes. The paucity of structural data for glycosyltransferases has been attributed to their membrane-associated character and low expression levels, but even with the relatively limited number of available structures it is possible to see emerging trends that offer a glimpse of the principles of enzyme structure.

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References

  1. Sharon N (2001) The conquest of the last frontier of molecular and cell biology. Biochimie 83(7):555

    CAS  Google Scholar 

  2. Fukuda M (1994) In: Fukuda M, Hindsgaul O (eds) Molecular Glycobiology: Frontiers in Molecular Biology. 3–18. Oxford University Press, Oxford

    Google Scholar 

  3. Schwartz NB (1982) In: Varma RS (ed) Glycosaminoglycans and Proteoglycans in Physiological and Pathological Processes of Body Systems. Karger, Basel, New York, p 41–54

    Google Scholar 

  4. Geetha-Habib M, Campbell SC, Schwartz NB (1984) Subcellular localization of the synthesis and glycosylation of chondroitin sulfate proteoglycan core protein. J Biol Chem 259(11):7300–7310

    CAS  Google Scholar 

  5. Frederiksen S, Malling H, Klenow H (1965) Isolation of 3′-Deoxyadenosine (Cordycepin) from the liquid medium of Cordyceps militaris (L. Ex. Fr.). Biochim Biophys Acta 95:189–193

    CAS  Google Scholar 

  6. Kolchinsky AM, Mirzabekov AD, Gilbert W, Li L (1976) Preferential protection of the minor groove of non-operator DNA by lac repressor against methylation by dimethyl sulphate. Nucleic Acids Res 3(1):11–18

    CAS  Google Scholar 

  7. Osborn MJ, D'Ari L (1964) Enzymatic incorporation of N-acetylglucosamine into cell wall lipopolysaccharide in a mutant strain of Salmonella typhimurium. Biochem Biophys Res Commun 16(6):568–575

    CAS  Google Scholar 

  8. Cooper D, Manley RS (1975) Cellulose synthesis by Acetobacter xylinum. I. Low molecular weight compounds present in the region of synthesis. Biochim Biophys Acta 381(1):78–96

    CAS  Google Scholar 

  9. McGuire EJ, Jourdian GW, Carlson DM, Roseman S (1965) Incorporation of D-galactose into glycoproteins. J Biol Chem 240(10):4112–4115

    CAS  Google Scholar 

  10. Moczar E, Moczar M (1970) A micro-method for the determination of hydroxylysine and its glycosylated derivatives. J Chromatogr 51(2):277–281

    CAS  Google Scholar 

  11. Apweiler R, Hermjakob H, Sharon N (1999) On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochim Biophys Acta 1473:4–8

    CAS  Google Scholar 

  12. Hunt LT, Dayhoff MO (1970) The occurrence in proteins of the tripeptides Asn-X-Ser and Asn-X-Thr and of bound carbohydrate. Biochem Biophys Res Commun 39(4):757–765

    CAS  Google Scholar 

  13. Sadler JE (1984) In: Ginsburg V, Robbins PW (eds) Biosynthesis of glycoproteins: formation of O-linked oligosaccarides. Biology of carbohydrates (2):199. Wiley, NY

    Google Scholar 

  14. Hart GW, Haltiwanger RS, Holt GD, Kelly WG (1989) Glycosylation in the nucleus and cytoplasm. Annu Rev Biochem 58:841–874

    CAS  Google Scholar 

  15. Lehle L, Schwarz RT (1976) Formation of dolichol monophosphate 2-deoxy-D-glucose and its interference with the glycosylation of mannoproteins in yeast. Eur J Biochem 67(1):239–245

    CAS  Google Scholar 

  16. Schaffer C, Dietrich K, Unger B, Scheberl A, Rainey FA, Kahlig H, Messner P (2000) A novel type of carbohydrate-protein linkage region in the tyrosine-bound S-layer glycan of Thermoanaerobacterium thermosaccharolyticum D120–70. Eur J Biochem 267(17):5482–5492

    CAS  Google Scholar 

  17. Spiro RG (1973) Glycoproteins. Adv Protein Chem 27:349–467

    CAS  Google Scholar 

  18. Allen AK, Desai NN, Neuberger A, Creeth JM (1978) Properties of potato lectin and the nature of its glycoprotein linkages. Biochem J 171:665–674

    CAS  Google Scholar 

  19. Shore G, Maclachlan GA (1975) The site of cellulose synthesis. Hormone treatment alters the intracellular location of alkali-insoluble β-1,4-glucan (cellulose) synthetase activities. J Cell Biol 64(3):557–571

    CAS  Google Scholar 

  20. Dahm K, Breuer H (1966) Partial purification of a soluble UDP-glucuronyltransferase from human intestine. Biochim Biophys Acta 113(2):404–406

    CAS  Google Scholar 

  21. Ikeda M, Wachi M, Jung HK, Ishino F, Matsuhashi M (1991) The Escherichia coli mraY gene encoding UDP-N-acetylmuramoyl-pentapeptide: undecaprenyl-phosphate phospho-N-acetylmuramoyl-pentapeptide transferase. J Bacteriol 173(3):1021–1026

    CAS  Google Scholar 

  22. Zgurskaya HI, Nikaido H (1999) AcrA is a highly asymmetric protein capable of spanning the periplasm. J Mol Biol 285(1):409–420

    CAS  Google Scholar 

  23. Prieto PA, Mukerji P, Kelder B, Erney R, Gonzalez D, Yun JS, Smith DF, Moremen KW, Nardelli C, Pierce M, Li Y, Chen X, Wagner TE, Cummings RD, Kopchick JJ (1995) Remodeling of mouse milk glycoconjugates by transgenic expression of a human glycosyltransferase. J Biol Chem 270(49):29515–29519

    CAS  Google Scholar 

  24. Palacpac NQ, Yoshida S, Sakai H, Kimura Y, Fujiyama K, Yoshida T, Seki T (1999) Stable expression of human β1,4-galactosyltransferase in plant cells modifies N-linked glycosylation patterns. Proc Natl Acad Sci USA 96(8):4692–4697

    CAS  Google Scholar 

  25. Dumon C, Priem B, Martin SL, Heyraud A, Bosso C, Samain E (2001) In vivo fucosylation of lacto-N-neotetraose and lacto-N-neohexaose by heterologous expression of Helicobacter pylori α-1,3 fucosyltransferase in engineered Escherichia coli. Glycoconj J 18(6):465–474

    CAS  Google Scholar 

  26. Shur BD, Evans S, Lu Q (1998) Cell surface galactosyltransferase: current issues. Glycoconj J 15(6):537–548

    CAS  Google Scholar 

  27. Takeuchi M, Inoue N, Strickland TW, Kubota M, Wada M, Shimizu R, Hoshi S, Kozutsumi H, Takasaki S, Kobata A (1989) Relationship between sugar chain structre and biological activity of recombinant human erythropoietin produced in chinese hamster overy cells. Proc Natl Acad Sci USA 86:7819–7822

    CAS  Google Scholar 

  28. Ohman R, Barker R, Hill R, Roseman S (1973) Glycosyltransferases – cellular studies. Birth Defects Orig Artic Ser 9(2):198–201

    CAS  Google Scholar 

  29. Bu'lock JD, Gregory H (1959) Pathways of sugar metabolism in relation to the biosynthesis of polyacetylenic antibiotics. Experientia 15:420–421

    Google Scholar 

  30. Reynolds PE, Somner EA (1990) Comparison of the target sites and mechanisms of action of glycopeptide and lipoglycodepsipeptide antibiotics. Drugs Exp Clin Res 16(8):385–389

    CAS  Google Scholar 

  31. Walsh CT, Losey HC, Freel Meyers CL (2003) Antibiotic glycosyltransferases. Biochem Soc Trans 31(Pt 3):487–492

    CAS  Google Scholar 

  32. Blumberg PM, Strominger JL (1974) Interaction of penicillin with the bacterial cell: penicillin-binding proteins and penicillin-sensitive enzymes. Bacteriol Rev 38(3):291–335

    CAS  Google Scholar 

  33. Gristina AG, Hobgood CD, Webb LX, Myrvik QN (1987) Adhesive colonization of biomaterials and antibiotic resistance. Biomaterials 8(6):423–426

    CAS  Google Scholar 

  34. Scholz S, Sonnenbichler J, Schafer W, Hensel R (1992) Di-myo-inositol-1,1′-phosphate: a new inositol phosphate isolated from Pyrococcus woesei. FEBS Lett 306(2–3):239–242

    CAS  Google Scholar 

  35. Clegg JS, Seitz P, Seitz W, Hazlewood CF (1982) Cellular responses to extreme water loss: the water-replacement hypothesis. Cryobiology 19(3):306–316

    CAS  Google Scholar 

  36. Shimma Y, Jigami Y (2004) Expression of human glycosyltransferase genes in yeast as a tool for enzymatic synthesis of sugar chain. Glycoconj J 21(1–2):75–78

    CAS  Google Scholar 

  37. Sandermann H Jr, Schmitt R, Eckey H, Bauknecht T (1991) Plant biochemistry of xenobiotics: isolation and properties of soybean O- and N-glucosyl and O- and N-malonyltransferases for chlorinated phenols and anilines. Arch Biochem Biophys 287(2):341–350

    CAS  Google Scholar 

  38. Chang HK, Zylstra GJ (1999) Role of quinolinate phosphoribosyl transferase in degradation of phthalate by Burkholderia cepacia DBO1. J Bacteriol 181(10):3069–3075

    CAS  Google Scholar 

  39. Brazier-Hicks M, Edwards R (2005) Functional importance of the family 1 glucosyltransferase UGT72B1 in the metabolism of xenobiotics in Arabidopsis thaliana. Plant J 42(4):556–566

    CAS  Google Scholar 

  40. Solenberg PJ, Matsushima P, Stack DR, Wilkie SC, Thompson RC, Baltz RH (1997) Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis. Chem Biol 4(3):195–202

    CAS  Google Scholar 

  41. Somoza JR, Skillman AG Jr, Munagala NR, Oshiro CM, Knegtel RM, Mpoke S, Fletterick RJ, Kuntz ID, Wang CC (1998) Rational design of novel antimicrobials: blocking purine salvage in a parasitic protozoan. Biochemistry 37(16):5344–5348

    CAS  Google Scholar 

  42. Gamble W (1975) Mechanism of action of hypolipidemic and herbicidal aryloxy acids. J Theor Biol 54(2):181–190

    CAS  Google Scholar 

  43. Edwards R, Del Buono D, Fordham M, Skipsey M, Brazier M, Dixon DP, Cummings I (2005) Differential induction of glutathione transferases and glucosyltransferases in wheat, maize and Arabidopsis thaliana by herbicide safeners. Z Naturforsch [C] 60(3–4):307–316

    CAS  Google Scholar 

  44. Luckow VA, Lee SC, Barry GF, Olins PO (1993) Efficient generation of infectious recombinant baculoviruses by site-specific transposon-mediated insertion of foreign genes into a baculovirus genome propagated in Escherichia coli. J Virol 67(8):4566–4579

    CAS  Google Scholar 

  45. Burkle A, Diefenbach J, Brabeck C, Beneke S (2005) Ageing and PARP. Pharmacol Res 52(1):93–99

    Google Scholar 

  46. Lloyd KO (2000) The chemistry and immunochemistry of blood group A, B, H, and Lewis antigens: past, present and future. Glycoconj J 17(7–9):531–541

    CAS  Google Scholar 

  47. Bucher P, Morel P, Buhler LH (2005) Xenotransplantation: an update on recent progress and future perspectives. Transpl Int 18(8):894–901

    Google Scholar 

  48. Davies GJ (2001) Sweet secrets of synthesis. Nat Struct Biol 8(2):98–100

    CAS  Google Scholar 

  49. Rupprath C, Schumacher T, Elling L (2005) Nucleotide deoxysugars: essential tools for the glycosylation engineering of novel bioactive compounds. Curr Med Chem 12(14):1637–1675

    CAS  Google Scholar 

  50. Seto NO, Palcic MM, Compston CA, Li H, Bundle DR, Narang SA (1997) Sequential interchange of four amino acids from blood group B to blood group A glycosyltransferase boosts catalytic activity and progressively modifies substrate recognition in human recombinant enzymes. J Biol Chem 272(22):14133–14138

    CAS  Google Scholar 

  51. Seto NO, Compston CA, Evans SV, Bundle DR, Narang SA, Palcic MM (1999) Donor substrate specificity of recombinant human blood group A, B and hybrid A/B glycosyltransferases expressed in Escherichia coli. Eur J Biochem 259(3):770–775

    CAS  Google Scholar 

  52. Marcus SL, Polakowski R, Seto NO, Leinala E, Borisova S, Blancher A, Roubinet F, Evans SV, Palcic MM (2003) A single point mutation reverses the donor specificity of human blood group B-synthesizing galactosyltransferase. J Biol Chem 278(14):12403–12405

    CAS  Google Scholar 

  53. Khatra BS, Herries DG, Brew K (1974) Some kinetic properties of human-milk galactosyl transferase. Eur J Biochem 44(2):537–560

    CAS  Google Scholar 

  54. Yoshida M, Itano N, Yamada Y, Kimata K (2000) In vitro synthesis of hyaluronan by a single protein derived from mouse HAS1 gene and characterization of amino acid residues essential for the activity. J Biol Chem 275(1):497–506

    CAS  Google Scholar 

  55. Campbell JA, Davies GJ, Bulone V, Henrissat B (1997) A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem J 326(Pt 3):929–939

    CAS  Google Scholar 

  56. Coutinho PM, Deleury E, Davies GJ, Henrissat B (2003) An evolving hierarchical family classification for glycosyltransferases. J Mol Biol 328(2):307–317

    CAS  Google Scholar 

  57. Rosen ML, Edman M, Sjostrom M, Wieslander A (2004) Recognition of fold and sugar linkage for glycosyltransferases by multivariate sequence analysis. J Biol Chem 279(37):38683–38692

    CAS  Google Scholar 

  58. Sinnott ML (1990) Catalytic mechanisms of enzymatic glycosyl transfer. Chem Rev 90:1171–1202

    CAS  Google Scholar 

  59. Paulson JC, Colley KJ (1989) Glycosyltransferases. Structure, localization, and control of cell type-specific glycosylation. Biol Chem 264(30):17615–17618

    CAS  Google Scholar 

  60. Bourne Y, Henrissat B (2001) Glycoside hydrolases and glycosyltransferases: families and functional modules. Curr Opin Struct Biol 11(5):593–600

    CAS  Google Scholar 

  61. Dodson E, Harding MM, Hodgkin DC, Rossmann MG (1966) The crystal structure of insulin. 3. Evidence for a 2-fold axis in rhombohedral zinc insulin. J Mol Biol 16(1):227–241

    Article  CAS  Google Scholar 

  62. Unligil UM, Rini JM (2000) Glycosyltransferase structure and mechanism. Curr Opin Struct Biol 10(5):510–517

    CAS  Google Scholar 

  63. Charnock SJ, Davies GJ (1999) Structure of the nucleotide-diphospho-sugar transferase, SpsA from Bacillus subtilis, in native and nucleotide-complexed forms. Biochemistry 38(20):6380–6385

    CAS  Google Scholar 

  64. Patenaude SI, Seto NO, Borisova SN, Szpacenko A, Marcus SL, Palcic MM, Evans SV (2002) The structural basis for specificity in human ABO(H) blood group biosynthesis. Nat Struct Biol 9(9):685–690

    CAS  Google Scholar 

  65. Mulichak AM, Losey HC, Lu W, Wawrzak Z, Walsh CT, Garavito RM (2003) Structure of the TDP-epi-vancosaminyltransferase GtfA from the chloroeremomycin biosynthetic pathway. Proc Natl Acad Sci USA 100(16):9238–9243

    CAS  Google Scholar 

  66. Liu J, Mushegian A (2003) Three monophyletic superfamilies account for the majority of the known glycosyltransferases. Protein Sci 12(7):1418–1431

    CAS  Google Scholar 

  67. Kikuchi N, Kwon YD, Gotoh M, Narimatsu H (2003) Comparison of glycosyltransferase families using the profile hidden Markov model. Biochem Biophys Res Commun 310(2):574–579

    CAS  Google Scholar 

  68. Chelsky D, Parsons SM (1975) Stereochemical course of the adenosine triphosphate phosphoribosyltransferase reaction in histidine biosynthesis. J Biol Chem 250(14):5669–5673

    CAS  Google Scholar 

  69. Howard S, He S, Withers SG (1998) Identification of the active site nucleophile in jack bean α-mannosidase using 5-fluoro-β-l-gulosyl fluoride. J Biol Chem 273(4):2067–2072

    CAS  Google Scholar 

  70. Numao S, Kuntz DA, Withers SG, Rose DR (2003) Insights into the mechanism of Drosophila melanogaster Golgi α-mannosidase II through the structural analysis of covalent reaction intermediates. J Biol Chem 278(48):48074–48083

    CAS  Google Scholar 

  71. Lairson LL, Chiu CP, Ly HD, He S, Wakarchuk WW, Strynadka NC, Withers SG (2004) Intermediate trapping on a mutant retaining α-galactosyltransferase identifies an unexpected aspartate residue. J Biol Chem 279(27):28339–28344

    CAS  Google Scholar 

  72. Persson K, Ly HD, Dieckelmann M, Wakarchuk WW, Withers SG, Strynadka NC (2001) Crystal structure of the retaining galactosyltransferase LgtC from Neisseria meningitidis in complex with donor and acceptor sugar analogs. Nat Struct Biol 8(2):166–175

    CAS  Google Scholar 

  73. Li TL, Choroba OW, Charles EH, Sandercock AM, Williams DH, Spencer JB (2001) Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of two unusual amino acids occurring in the vancomycin group of antibiotics. Chem Commun (Cambridge) 18:1752–1753

    Google Scholar 

  74. Pedersen LC, Darden TA, Negishi M (2002) Crystal structure of β1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA. J Biol Chem 277(24):21869–21873

    CAS  Google Scholar 

  75. Hubbard BK, Walsh CT (2003) Vancomycin assembly: nature's way. Angew Chem Int Ed 2(7):730–765

    Google Scholar 

  76. Yazer MH, Palcic MM (2005) The importance of disordered loops in ABO glycosyltransferases. Transfus Med Rev 19(3):210–216

    Google Scholar 

  77. Breton C, Bettler E, Joziasse DH, Geremia RA, Imberty A (1998) Sequence-function relationships of prokaryotic and eukaryotic galactosyltransferases. J Biochem (Tokyo) 123(6):1000–1009

    CAS  Google Scholar 

  78. Busch C, Hofmann F, Selzer J, Munro S, Jeckel D, Aktories K (1998) A common motif of eukaryotic glycosyltransferases is essential for the enzyme activity of large clostridial cytotoxins. J Biol Chem 273(31):19566–19572

    CAS  Google Scholar 

  79. Wiggins CA, Munro S (1998) Activity of the yeast MNN1 α-1,3-mannosyltransferase requires a motif conserved in many other families of glycosyltransferases. Proc Natl Acad Sci USA 95(14):7945–7950

    CAS  Google Scholar 

  80. Shibayama K, Ohsuka S, Sato K, Yokoyama K, Horii T, Ohta M (1999) Four critical aspartic acid residues potentially involved in the catalytic mechanism of Escherichia coli K-12 WaaR. FEMS Microbiol Lett 174(1):105–109

    CAS  Google Scholar 

  81. Hodson N, Griffiths G, Cook N, Pourhossein M, Gottfridson E, Lind T, Lidholt K, Roberts IS (2000) Identification that KfiA, a protein essential for the biosynthesis of the Escherichia coli K5 capsular polysaccharide, is an α-UDP-GlcNAc glycosyltransferase. The formation of a membrane-associated K5 biosynthetic complex requires KfiA, KfiB, and KfiC. J Biol Chem 275(35):27311–27315

    CAS  Google Scholar 

  82. Pak JE, Arnoux P, Zhou S, Sivarajah P, Satkunarajah M, Xing X, Rini JM (2006) X-ray crystal structure of leukocyte type core 2 beta 1,6-N-acetylglucosaminyltransferase. Evidence for a convergence of metal ion-independent glycosyltransferase mechanism. J Biol Chem 281(36):26693–26701

    CAS  Google Scholar 

  83. Lobsanov YD, Romero PA, Sleno B, Yu B, Yip P, Herscovics A, Howell PL (2004) Structure of Kre2p/Mnt1p: a yeast α1,2-mannosyltransferase involved in mannoprotein biosynthesis. J Biol Chem 279(17):17921–17931

    CAS  Google Scholar 

  84. Chiu CP, Watts AG, Lairson LL, Gilbert M, Lim D, Wakarchuk WW, Withers SG, Strynadka NC (2004) Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog. Nat Struct Mol Biol 11(2):163–170

    CAS  Google Scholar 

  85. Kamst E, Bakkers J, Quaedvlieg NE, Pilling J, Kijne JW, Lugtenberg BJ, Spaink HP (1999) Chitin oligosaccharide synthesis by rhizobia and zebrafish embryos starts by glycosyl transfer to O4 of the reducing-terminal residue. Biochemistry 38(13):4045–4052

    CAS  Google Scholar 

  86. Itano N, Kimata K (1996) Expression cloning and molecular characterization of HAS protein, a eukaryotic hyaluronan synthase. J Biol Chem 271(17):9875–9878

    CAS  Google Scholar 

  87. Coutinho PM, Henrissat B (1999) Carbohydrate-active enzymes: an integrated approach. In: Gilbert HJ, Davies GJ, Svensson B, Henrissat B (eds) Recent Advances in Carbohydrate Engineering. 3–12. Royal Society of Chemistry, Cambridge

    Google Scholar 

  88. Gillespie SH (1989) Aspects of pneumococcal infection including bacterial virulence, host response and vaccination. J Med Microbiol 28(4):237–248

    Article  CAS  Google Scholar 

  89. Tarbouriech N, Charnock SJ, Davies GJ (2001) Three-dimensional structures of the Mn and Mg dTDP complexes of the family GT-2 glycosyltransferase SpsA: a comparison with related NDP-sugar glycosyltransferases. J Mol Biol 314(4):655–661

    CAS  Google Scholar 

  90. Focia PJ, Craig SP 3rd, Eakin AE (1998) Approaching the transition state in the crystal structure of a phosphoribosyltransferase. Biochemistry 37(49):17120–17127

    CAS  Google Scholar 

  91. Hagen FK, Hazes B, Raffo R, deSa D, Tabak LA (1999) Structure-function analysis of the UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase. Essential residues lie in a predicted active site cleft resembling a lactose repressor fold. J Biol Chem 274(10):6797–6803

    CAS  Google Scholar 

  92. Ramakrishnan B, Balaji PV, Qasba PK (2002) Crystal structure of β1,4-galactosyltransferase complex with UDP-Gal reveals an oligosaccharide acceptor binding site. J Mol Biol 318(2):491–502

    CAS  Google Scholar 

  93. Gastinel LN, Cambillau C, Bourne Y (1999) Crystal structures of the bovine β4-galactosyltransferase catalytic domain and its complex with uridine diphosphogalactose. EMBO J 18(13):3546–3557

    CAS  Google Scholar 

  94. Boeggeman EE, Ramakrishnan B, Qasba PK (2003) N-terminal stem region of bovine and human β1,4-galactosyltransferase I increases the in vitro folding efficiency of their catalytic domain from inclusion bodies. Protein Expr Purif 30(2):219–229

    CAS  Google Scholar 

  95. Powell JT, Brew K (1976) Metal ion activation of galactosyltransferase. J Biol Chem 251(12):3645–3652

    CAS  Google Scholar 

  96. O'Keeffe ET, Hill RL, Bell JE (1980) Active site of bovine galactosyltransferase: kinetic and fluorescence studies. Biochemistry 19(22):4954–4962

    Google Scholar 

  97. Ramakrishnan B, Shah PS, Qasba PK (2001) α-Lactalbumin (LA) stimulates milk β-1,4-galactosyltransferase I (β4Gal-T1) to transfer glucose from UDP-glucose to N-acetylglucosamine. Crystal structure of β4Gal-T1 x LA complex with UDP-Glc. J Biol Chem 276(40):37665–37671

    CAS  Google Scholar 

  98. Brodbeck U, Denton WL, Tanahashi N, Ebner KE (1967) The isolation and identification of the B protein of lactose synthetase as α-lactalbumin. J Biol Chem 242(7):1391–1397

    CAS  Google Scholar 

  99. Qasba PK, Kumar S (1997) Molecular divergence of lysozymes and α-lactalbumin. Crit Rev Biochem Mol Biol 32(4):255–306

    CAS  Google Scholar 

  100. Ramakrishnan B, Qasba PK (2001) Crystal structure of lactose synthase reveals a large conformational change in its catalytic component, the β1,4-galactosyltransferase-I. J Mol Biol 310(1):205–218

    CAS  Google Scholar 

  101. Cinquin C, Le Blay G, Fliss I, Lacroix C (2004) Immobilization of infant fecal microbiota and utilization in an in vitro colonic fermentation model. Microb Ecol 48(1):128–138

    CAS  Google Scholar 

  102. Pedersen LC, Tsuchida K, Kitagawa H, Sugahara K, Darden TA, Negishi M (2000) Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human glucuronyltransferase I. J Biol Chem 275(44):34580–34585

    CAS  Google Scholar 

  103. Helting T, Rodén L (1969) Biosynthesis of Chondroitin Sulfate: Glucuronosyl Transfer In The Formation Of The Carbohydrate-Protein Linkage Region. J Biol Chem 244(10):2799–2805

    CAS  Google Scholar 

  104. Kakuda S, Shiba T, Ishiguro M, Tagawa H, Oka S, Kajihara Y, Kawasaki T, Wakatsuki S, Kato R (2004) Structural basis for acceptor substrate recognition of a human glucuronyltransferase, GlcAT-P, an enzyme critical in the biosynthesis of the carbohydrate epitope HNK-1. J Biol Chem 279(21):22693–22703

    CAS  Google Scholar 

  105. Tone Y, Kitagawa H, Imiya K, Oka S, Kawasaki T, Sugahara K (1999) Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans. FEBS Lett 459(3):415–420

    CAS  Google Scholar 

  106. Oka S, Terayama K, Kawashima C, Kawasaki T (1992) A novel glucuronyltransferase in nervous system presumably associated with the biosynthesis of HNK-1 carbohydrate epitope on glycoproteins. J Biol Chem 267(32):22711–22714

    CAS  Google Scholar 

  107. Chou DK, Ilyas AA, Evans JE, Costello C, Quarles RH, Jungalwala FB (1986) Structure of sulfated glucuronyl glycolipids in the nervous system reacting with HNK-1 antibody and some IgM paraproteins in neuropathy. J Biol Chem 261(25):11717–11725

    CAS  Google Scholar 

  108. Jeffries AR, Mungall AJ, Dawson E, Halls K, Langford CF, Murray RM, Dunham I, Powell JF (2003) β-1,3-Glucuronyltransferase-1 gene implicated as a candidate for a schizophrenia-like psychosis through molecular analysis of a balanced translocation. Mol Psychiatry 8(7):654–663

    CAS  Google Scholar 

  109. Tukey RH, Strassburg CP (2000) Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581–616

    CAS  Google Scholar 

  110. Wysocki SJ, Segal W (1972) Influence of thyroid hormones on enzyme activities of myelinating rat central-nervous tissues. Eur J Biochem 28(2):183–189

    CAS  Google Scholar 

  111. Mulichak AM, Losey HC, Walsh CT, Garavito RM (2001) Structure of the UDP-glucosyltransferase GtfB that modifies the heptapeptide aglycone in the biosynthesis of vancomycin group antibiotics. Structure (Cambridge) 9(7):547–557

    CAS  Google Scholar 

  112. Mulichak AM, Lu W, Losey HC, Walsh CT, Garavito RM (2004) Crystal structure of vancosaminyltransferase GtfD from the vancomycin biosynthetic pathway: interactions with acceptor and nucleotide ligands. Biochemistry 43(18):5170–5180

    CAS  Google Scholar 

  113. Freund E, Vitali F, Linden A, Robinson JA (2000) Solid-phase synthesis using (Allyloxy)carbonyl(Alloc) chemistry of a putative heptapeptide intermediate in vancomycin biosynthesis containing m-chloro-3-hydroxytyrosine. Helv Chim Acta 83:2572–2579

    CAS  Google Scholar 

  114. Appel GB, Neu HC (1977) The nephrotoxicity of antimicrobial agents. N Engl J Med 296:722–728

    Article  CAS  Google Scholar 

  115. Schwalbe RS, Stapleton JT, Gilligan PH (1987) Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med 316(15):927–931

    Article  CAS  Google Scholar 

  116. Martone WJ (1998) Spread of vancomycin-resistant enterococci: why did it happen in the United States? Infect Control Hosp Epidemiol 19(8):539–545

    Article  CAS  Google Scholar 

  117. Ramadhan AA, Hegedus E (2005) Survivability of vancomycin resistant enterococci and fitness cost of vancomycin resistance acquisition. J Clin Pathol 58(7):744–746

    CAS  Google Scholar 

  118. Jones RN, Barrett MS, Erwin ME (1997) In vitro activity and spectrum of LY333328, a novel glycopeptide derivative. Antimicrob Agents Chemother 41(2):488–493

    CAS  Google Scholar 

  119. Rodriguez MJ, Snyder NJ, Zweifel MJ, Wilkie SC, Stack DR, Cooper RD, Nicas TI, Mullen DL, Butler TF, Thompson RC (1998) Novel glycopeptide antibiotics: N-alkylated derivatives active against vancomycin-resistant enterococci. J Antibiot (Tokyo) 51(6):560–569

    CAS  Google Scholar 

  120. Brown JP, Feeney J, Burgen AS (1975) A nuclear magnetic resonance study of the interaction between vanomycin and acetyl-D-alanyl-D-alanin in aqueous solution. Mol Pharmacol 11(2):119–125

    CAS  Google Scholar 

  121. Josse J, Kornberg A (1962) Glycosylation of deoxyribonucleic acid, III, alpha- and beta-Glycosyl transferases from T4-infected Escherichia coli. J Biol Chem 237:1968–1976

    CAS  Google Scholar 

  122. Morera S, Imberty A, Aschke-Sonnenborn U, Ruger W, Freemont PS (1999) T4 phage β-glucosyltransferase: substrate binding and proposed catalytic mechanism. J Mol Biol 292(3):717–730

    CAS  Google Scholar 

  123. Lariviere L, Morera S (2002) A base-flipping mechanism for the T4 phage β-glucosyltransferase and identification of a transition-state analog. J Mol Biol 324(3):483–490

    CAS  Google Scholar 

  124. Lariviere L, Morera S (2004) Structural evidence of a passive base-flipping mechanism for beta-glucosyltransferase. J Biol Chem 279(33):34715–34720

    CAS  Google Scholar 

  125. Lariviere L, Gueguen-Chaignon V, Morera S (2003) Crystal structures of the T4 phage β-glucosyltransferase and the D100A mutant in complex with UDP-glucose: glucose binding and identification of the catalytic base for a direct displacement mechanism. J Mol Biol 330(5):1077–1086

    CAS  Google Scholar 

  126. Morera S, Lariviere L, Kurzeck J, Aschke-Sonnenborn U, Freemont PS, Janin J, Ruger W (2001) High resolution crystal structures of T4 phage β-glucosyltransferase: induced fit and effect of substrate and metal binding. J Mol Biol 311(3):569–577

    CAS  Google Scholar 

  127. Vrielink A, Ruger W, Driessen HP, Freemont PS (1994) Crystal structure of the DNA modifying enzyme β-glucosyltransferase in the presence and absence of the substrate uridine diphosphoglucose. EMBO J 13(15):3413–3422

    CAS  Google Scholar 

  128. Watkins WM, Morgan WT (1957) Specific inhibition studies relating to the Lewis blood-group system. Nature 180:1038–1040

    CAS  Google Scholar 

  129. Landsteiner K (1901) Ueber Agglutinationserscheinungen normalen menschlichen Blutes. Wien Klin Wochenschr 14:1132–1134

    Google Scholar 

  130. Lee HJ, Barry CH, Borisova SN, Seto NO, Zheng RB, Blancher A, Evans SV, Palcic MM (2005) Structural basis for the inactivity of human blood group O2 glycosyltransferase. J Biol Chem 280(1):525–529

    CAS  Google Scholar 

  131. Clausen H, White T, Takio K, Titani K, Stroud M, Holmes E, Karkov J, Thim L, Hakomori S (1990) Isolation to homogeneity and partial characterization of a histo-blood group A defined Fuc α1–2Gal α1–3-N-acetylgalactosaminyltransferase from human lung tissue. J Biol Chem 265(2):1139–1145

    CAS  Google Scholar 

  132. Yamamoto F, Clausen H, White T, Marken J, Hakomori S (1990) Molecular genetic basis of the histo-blood group ABO system. Nature 345:229–233

    CAS  Google Scholar 

  133. Nguyen HP, Seto NO, Cai Y, Leinala EK, Borisova SN, Palcic MM, Evans SV (2003) The influence of an intramolecular hydrogen bond in differential recognition of inhibitory acceptor analogs by human ABO(H) blood group A and B glycosyltransferases. J Biol Chem 278(49):49191–49195

    CAS  Google Scholar 

  134. Zak BM, Crawford BE, Esko JD (2002) Hereditary multiple exostoses and heparan sulfate polymerization. Biochim Biophys Acta 1573(3):346–355

    CAS  Google Scholar 

  135. Pedersen LC, Dong J, Taniguchi F, Kitagawa H, Krahn JM, Pedersen LG, Sugahara K, Negishi M (2003) Crystal structure of an α1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis. J Biol Chem 278(16):14420–14428

    CAS  Google Scholar 

  136. Kitagawa H, Shimakawa H, Sugahara K (1999) The tumor suppressor EXT-like gene EXTL2 encodes an α1,4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region. J Biol Chem 274(20):13933–13937

    CAS  Google Scholar 

  137. Faria TQ, Lima JC, Bastos M, Macanita AL, Santos H (2004) Protein stabilization by osmolytes from hyperthermophiles: effect of mannosylglycerate on the thermal unfolding of recombinant nuclease a from Staphylococcus aureus studied by picosecond time-resolved fluorescence and calorimetry. J Biol Chem 279(47):48680–48691

    CAS  Google Scholar 

  138. Davis-Searles PR, Saunders AJ, Erie DA, Winzor DJ, Pielak GJ (2001) Interpreting the effects of small uncharged solutes on protein-folding equilibria. Annu Rev Biophys Biomol Struct 30:271–306

    CAS  Google Scholar 

  139. Martins LO, Empadinhas N, Marugg JD, Miguel C, Ferreira C, da Costa MS, Santos H (1999) Biosynthesis of mannosylglycerate in the thermophilic bacterium Rhodothermus marinus. Biochemical and genetic characterization of a mannosylglycerate synthase. J Biol Chem 274(50):35407–35414

    CAS  Google Scholar 

  140. Flint J, Taylor E, Yang M, Bolam DN, Tailford LE, Martinez-Fleites C, Dodson EJ, Davis BG, Gilbert HJ, Davies GJ (2005) Structural dissection and high-throughput screening of mannosylglycerate synthase. Nat Struct Mol Biol 12(7):608–614

    CAS  Google Scholar 

  141. Frydman RB, Cardini CE (1964) Biosynthesis of phytoglycogen from adenosine diphosphate D-glucose in sweet corn. Biochem Biophys Res Commun 14:353–357

    CAS  Google Scholar 

  142. Shukla RN, Sanwal GG (1971) Studies on UDP-glucose: D-fructose 2-glucosyltransferase from tapioca tuber. Arch Biochem Biophys 142(1):303–309

    CAS  Google Scholar 

  143. Goldemberg SH (1962) Specificity of uridine diphosphate glucose-glycogen glucosyltransferase. Biochim Biophys Acta 56:357–359

    CAS  Google Scholar 

  144. Cao Y, Steinrauf LK, Roach PJ (1995) Mechanism of glycogenin self-glucosylation. Arch Biochem Biophys 319(1):293–298

    CAS  Google Scholar 

  145. Barker SA, Bourne E, Peat S (1949) The enzymic synthesis and degradation of starch. Part IV The purification and storage of the Q-enzyme of the potato. J Chem Soc 1:1705–1711

    Google Scholar 

  146. Henrissat B (1991) A classification of glycosyl hydrolases based on amino-acid sequence similarities. Biochem J 280:309–316

    CAS  Google Scholar 

  147. Cori GT (1952) Glycogen structure and enzyme deficiencies in glycogen storage disease. Harvey Lect 48:145–171

    Google Scholar 

  148. Buschiazzo A, Ugalde JE, Guerin ME, Shepard W, Ugalde RA, Alzari PM (2004) Crystal structure of glycogen synthase: homologous enzymes catalyze glycogen synthesis and degradation. EMBO J 23(16):3196–3205

    CAS  Google Scholar 

  149. Bachrach BE, Weinstein DA, Orho-Melander M, Burgess A, Wolfsdorf JI (2002) Glycogen synthase deficiency (glycogen storage disease type 0) presenting with hyperglycemia and glucosuria: report of three new mutations. J Pediatr 140(6):781–783

    CAS  Google Scholar 

  150. Iwahashi H, Shimizu H, Odani M, Komatsu Y (2003) Piezophysiology of genome wide gene expression levels in the yeast Saccharomyces cerevisiae. Extremophiles 7(4):291–298

    CAS  Google Scholar 

  151. Porchia AC, Curatti L, Salerno GL (1999) Sucrose metabolism in cyanobacteria: sucrose synthase from Anabaena sp. strain PCC 7119 is remarkably different from the plant enzymes with respect to substrate affinity and amino-terminal sequence. Planta 210(1):34–40

    CAS  Google Scholar 

  152. Singer MA, Lindquist S (1998) Thermotolerance in Saccharomyces cerevisiae: the yin and yang of trehalose. Trends Biotechnol 16:460–468

    CAS  Google Scholar 

  153. Sahara T, Goda T, Ohgiya S (2002) Comprehensive expression analysis of time-dependent genetic responses in yeast cells to low temperature. J Biol Chem 277(51):50015–50021

    CAS  Google Scholar 

  154. Chen Q, Ma E, Behar KL, Xu T, Haddad GG (2002) Role of trehalose phosphate synthase in anoxia tolerance and development in Drosophila melanogaster. J Biol Chem 277(5):3274–3279

    CAS  Google Scholar 

  155. Benaroudj N, Lee DH, Goldberg AL (2001) Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J Biol Chem 276:24261–24267

    CAS  Google Scholar 

  156. Pereira Ede J, Panek AD, Eleutherio EC (2003) Protection against oxidation during dehydration of yeast. Cell Stress Chaperones 8(2):120–124

    Google Scholar 

  157. Birch GG (1963) Trehalose. Adv Carb Chem 18:201–225

    CAS  Google Scholar 

  158. Elbein AD (1974) The metabolism of α,α-trehalose. Adv Carbohydr Chem Biochem 30:227–256

    Article  CAS  Google Scholar 

  159. Kaushik JK, Bhat R (2003) Why is trehalose an exceptional protein stabilizer? An analysis of the thermal stability of proteins in the presence of the compatible osmolyte trehalose. J Biol Chem 278(29):26458–26465

    CAS  Google Scholar 

  160. De Smet KA, Weston A, Brown IN, Young DB, Robertson BD (2000) Three pathways for trehalose biosynthesis in mycobacteria. Microbiology 146(Pt 1):199–208

    Google Scholar 

  161. Gibson RP, Turkenburg JP, Charnock SJ, Lloyd R, Davies GJ (2002) Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA. Chem Biol 9(12):1337–1346

    CAS  Google Scholar 

  162. Gibson RP, Tarling CA, Roberts S, Withers SG, Davies GJ (2004) The donor subsite of trehalose-6-phosphate synthase: binary complexes with UDP-glucose and UDP-2-deoxy-2-fluoro-glucose at 2 Åresolution. J Biol Chem 279(3):1950–1955

    CAS  Google Scholar 

  163. Moore JE, Corcoran D, Dooley JS, Fanning S, Lucey B, Matsuda M, McDowell DA, Megraud F, Millar BC, O'Mahony R, O'Riordan L, O'Rourke M, Rao JR, Rooney PJ, Sails A, Whyte P (2005) Campylobacter Vet Res 36(3):351–382

    CAS  Google Scholar 

  164. Evans SV (1993) SETOR: hardware-lighted three-dimensional solid model representations of macromolecules. J Mol Graph 11(2):134–138

    CAS  Google Scholar 

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  1. Department of Biochemistry & Microbiology, University of Victoria, Victoria, BC, Canada

    Brock Schuman, Javier A. Alfaro & Stephen V. Evans

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  1. Brock Schuman
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Schuman, B., Alfaro, J.A., Evans, S.V. (2006). Glycosyltransferase Structure and Function. In: Peters, T. (eds) Bioactive Conformation I. Topics in Current Chemistry, vol 272. Springer, Berlin, Heidelberg . https://doi.org/10.1007/128_2006_089

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