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The acceptor specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases

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Abstract

The in vitro and in vivo specificity of the family of peptide:N-acetylgalactosaminyltransferases (GalNAcT) is analyzed on the basis of the reactivity and/or inhibitory activity of peptides and protein segments. The transferases appear to be multi-substrate enzymes with extended active sites containing a least nine subsites that interact cooperatively with a linear segment of at least nine amino acid residues on the acceptor polypeptide. Functional acceptor sites are located on the surface of the protein and extended conformations (β-strand conformation) are preferred. The acceptor specificity of GalNAc-T can be predicted from the primary structure of the acceptor peptide with an accuracy of 70 to 80%. The same GalNAc-T enzymes catalyze the glycosylation of both serine and threonine residues. The higher in vitro catalytic efficiency toward threonine versus serine is the result of enhanced binding as well as increased reaction velocity, both effects being the result of steric interactions between the active site of the enzyme and the methyl group of threonine. Results from substrate binding studies suggest that GalNAc-T catalyzed transfer proceeds via an ordered sequential mechanism.

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References

  1. Sadler JE (1984) In Biosynthesis of Glycoproteins: Formation of O-linked Oligosaccharides (Ginsburg V, Robbins, PW, eds) pp 199–288. New York: JE Wiley.

    Google Scholar 

  2. Schachter H, Brockhausen I (1993) In Glycoconjugates: Composition, Structure and Function (Allen HJ, Kisailus EC, eds) pp 263–332. New York: Marcel Dekker, Inc.

    Google Scholar 

  3. Roseman S (1970) Chem Phys Lipids 5: 270–97.

    Google Scholar 

  4. Seidah NG, Chretien M (1981) Proc Natl Acad Sci USA 78: 4236–40.

    Google Scholar 

  5. Titani K, Kumar S, Takio K, Ericsson LH, Wade RD, Ashida K, Walsh KA, Chopek MW, Sadler JE, Fujikawa K (1986) Biochemistry 25: 3171–84.

    Google Scholar 

  6. Rohani A, Zannis VI (1988) J Biol Chem 263: 17925–32.

    Google Scholar 

  7. Wernette-Hammond ME, Lauer SJ, Corsini A, Walker D, Taylor JM, Rall SC, Jr (1989) J Biol Chem 264: 9094–101.

    Google Scholar 

  8. Hayes GR, Enns CA, Lucas JJ (1992) Glycobiology 2: 355–9.

    Google Scholar 

  9. Steiner V, Knecht R, Börnsen O, Gassman E, Stone SR, Raschdorf F, Schlaeppi J-M, Maschler R (1992) Biochemistry 31: 2294–98.

    Google Scholar 

  10. Shimizu N, Hara H, Sogabe T, Sakai H, Ihara I, Inoue H, Nakamura T, Shimizu S (1992) Biochim. Biophys. Res. Commun. 189, 1329–35.

    Google Scholar 

  11. Do S-I, Cummings RD (1992) Glycobiology 2, 345–53.

    Google Scholar 

  12. Kim H, Yamaguchi Y, Masuda K, Matsunaga C, Yamamoto K, Irimura T, Takahashi N, Arata Y (1994) J Biol Chem 269: 12345–50.

    Google Scholar 

  13. Pirie-Shepherd S, Stevens RD, Andon NL, Enghild JJ, Pizzo SV (1997) J Biol Chem 272: 7408–11.

    Google Scholar 

  14. Devine PL, McKenzie FC (1992) BioEssays 14: 619–25.

    Google Scholar 

  15. Strous GJ, Dekker J (1992) Crit Rev Biochem Mol Biol 27: 57–92.

    Google Scholar 

  16. Van Klinken BJ-W, Dekker J, Büller HA, Einerhand AWC (1995) Am J Physiol 269: G613–27.

    Google Scholar 

  17. Jentoft N (1990) TIBS 15: 291–94.

    Google Scholar 

  18. Elhammer ÅP, Poorman RA, Brown E, Maggiora LL, Hoogerheide JG, Kézdy FJ (1993) J Biol Chem 268: 10029–38.

    Google Scholar 

  19. Hansen JE, Lund O, Engelbrecht J, Bohr H, Nielsen JO, Hansen J-ES, Brunak S (1995) Biochem J 308: 801–13.

    Google Scholar 

  20. Butenhof KJ, Gerken TA (1993) Biochemistry 32: 2650–63.

    Google Scholar 

  21. Gerken TA, Owens CL, Pasumarthy M (1997) J Biol Chem 272: 9709–19.

    Google Scholar 

  22. Neumann GM, Marinaro JA, Bach LA (1998) Biochemistry 37: 6572–85.

    Google Scholar 

  23. Marth JD (1996) Glycobiology 6, 701–5.

    Google Scholar 

  24. Homa FL, Hollander T, Lehman DJ, Thomsen DR, Elhammer ÅP (1993) J Biol Chem 268: 12609–16.

    Google Scholar 

  25. Hagen FK, Van Wuyckhuyse B, Tabak LA (1993) J Biol Chem 268: 18960–65.

    Google Scholar 

  26. White T, Bennett EP, Takio K, Sørensen T, Bonding N, Clausen H (1995) J Biol Chem 270: 24156–65.

    Google Scholar 

  27. Bennett EP, Hassan H, Clausen H (1996) J Biol Chem 271: 17006–12.

    Google Scholar 

  28. Hagen FK, Ten Hagen KG, Beres TM, Balys MM, Van Wuyckhuyse BC, Tabak LA (1997) J Biol Chem 272: 13843–48.

    Google Scholar 

  29. Ten Hagen KG, Hagen FK, Balys MM, Beres TM, Van Wuyckhuyse B, Tabak LA (1998) J Biol Chem 273: 27749–54.

    Google Scholar 

  30. Wandall HH, Hassan H, Mirgorodskaya E, Kristensen AK, Roepstorff P, Bennett EP, Nielsen PA, Hollingsworth MA, Burchell J, Taylor-Papadimitriou J, Clausen H (1997) J Biol Chem 272: 23503–14.

    Google Scholar 

  31. Clausen H, Bennett EP (1996) Glycobiology 6: 635–46.

    Google Scholar 

  32. Tooze SA, Tooze J, Warren G (1988) J Cell Biol 106: 1475–87.

    Google Scholar 

  33. Pathak RK, Merkle RK, Cummings RD, Goldstein JL, Brown MS, Anderson RGW (1988) J Cell Biol 106: 1831–41.

    Google Scholar 

  34. Schweizer A, Clausen H, van Meer G, Hauri H-P (1994) J Biol Chem 269: 4035–41.

    Google Scholar 

  35. Johnson DC, Spear PG (1983) Cell 32: 987–97.

    Google Scholar 

  36. Roth J (1984) J Cell Biol 98, 399–406.

    Google Scholar 

  37. Elhammer Å, Kornfeld S (1984) J Cell Biol 98, 327–331.

    Google Scholar 

  38. Deschuyteneer M, Eckhardt AE, Roth J, Hill RL (1988) J Biol Chem 263: 2452–59.

    Google Scholar 

  39. Ulmer JB, Palade GE (1989) Proc Natl Acad Sci 86: 6992–96.

    Google Scholar 

  40. Piller V, Piller F, Fukuda M (1990) J Biol Chem 265: 9264–71.

    Google Scholar 

  41. Roth J, Wang Y, Eckhardt AE, Hill RL (1994) Proc Natl Acad Sci 91: 8935–39. 42 Abeijon C, Hirschberg CB (1987) J Biol Chem 262: 4153–59.

    Google Scholar 

  42. Abeijon C, Mandon EC, Hirschberg CB (1997) TIBS 22: 203–7. 44 Nehrke K, Ten Hagen KG, Hagen FK, Tabak LA (1997) Glycobiology 7: 1053–60.

    Google Scholar 

  43. Hagen FK, Van Wuyckhuyse B, Tabak LA (1993) J Biol Chem 268: 18960–65.

    Google Scholar 

  44. Kearns AE, Campbell SC, Westley J, Schwartz NB (1991) Biochemistry 30: 7477–83.

    Google Scholar 

  45. Hagopian A, Eylar EH (1968) Arch Biochem Biophys 128: 422–33.

    Google Scholar 

  46. Hagopian A, Westall FC, Whitehead JS, Eylar EH (1971) J Biol Chem 246: 2519–23.

    Google Scholar 

  47. Hill HD, Schwyzer M, Steinman HM, Hill RL (1977) J Biol Chem 252: 3799–804.

    Google Scholar 

  48. Young JD, Tsuchiya D, Sandlin DE, Holroyde MJ (1979) Biochemistry 18: 4444–48.

    Google Scholar 

  49. Briand JP, Andrews SP Jr., Cahill E, Conway NA, Young JD (1981) J Biol Chem 256: 12205–207.

    Google Scholar 

  50. Cruz TF, Moscarello MA (1983) Biochim Biophys Acta 760: 403–10.

    Google Scholar 

  51. Wang Y, Abernethy JL, Eckhardt AE, Hill RL (1992) J Biol Chem 267: 12709–16.

    Google Scholar 

  52. O'Connell B, Tabak LA, Ramasubbu N (1991) Biochem Biophys Res Commun 180: 1024–30.

    Google Scholar 

  53. O'Connel BC, Hagen FK, Tabak LA (1992) J Biol Chem 267: 25010–18.

    Google Scholar 

  54. O'Connel BC, Tabak LA (1993) J Dent Res 72: 1554–58.

    Google Scholar 

  55. Wang Y, Agrwal N, Eckhardt AE, Stevens RD, Hill RL (1993) J Biol Chem 268: 22979–83. 58 Nishimori I, Johnson NR, Sanderso SD, Perini F, Mountjoy K, Cerny RL, Gross ML, Hollingsworth MA (1994) J Biol Chem 269: 16123–30.

    Google Scholar 

  56. Nishimori I, Perini F, Mountjoy KP, Sanderson SD, Johnson N, Cerny RL, Gross ML, Fontenot JD, Hollingsworth MA (1994) Cancer Res 54: 3738–44.

    Google Scholar 

  57. Wragg S, Hagen FK, Tabak LA (1995) J Biol Chem 270: 16947–54.

    Google Scholar 

  58. Stadie TRE, Chai W, Lawson AM, Byfield PGH, Hanisch F-G (1995) Eur J Biochem 229: 140–47.

    Google Scholar 

  59. Brockhausen I, D, Brockhausen J, Peters S, Bielfeldt T, Kleen A, Paulsen H, Meldal M, Hagen F, Tabak LA (1996) Glycoconj J 13: 849–56.

    Google Scholar 

  60. Yoshida A, Suzuki M, Ikenaga H, Takeuchi M (1997) J Biol Chem 272: 16884–88.

    Google Scholar 

  61. Sugahara T, Pixley MR, Fares F, Boime I (1996) J Biol Chem 271: 20797–804.

    Google Scholar 

  62. Kornfeld R, Kornfeld S (1985) Ann Rev Biochem 54: 631–64.

    Google Scholar 

  63. Gooley AA, Classon BJ, Marschalek R, Williams KL (1991) Biochem Biophys Res Commun 178: 1194–201

    Google Scholar 

  64. Pisano A, Redmond JW, Williams KL, Gooley AA (1993)Glycobiology 3: 429–35.

    Google Scholar 

  65. Pisano A, Packer NH, Redmond JW, Williams KL, Gooley AA (1994) Glycobiology 4: 837–44.

    Google Scholar 

  66. Gooley AA, Williams KL (1994) Glycobiology 4: 413–17.

    Google Scholar 

  67. Sugahara T, Pixley MR, Fares F, Boime I (1996) J Biol Chem 271: 20797–804.

    Google Scholar 

  68. Chou K-C, Zhang C-T, Kézdy FJ, Poorman RA (1995) Proteins 21: 118–26.

    Google Scholar 

  69. Hansen JE, Lund O, Tolstrup N, Gooley AA, Williams KL, Brunak S (1997) Glycoconj J 15: 115–30.

    Google Scholar 

  70. Nehrke K, Hagen FK, Tabak LA (1996) J Biol Chem 271: 7061–65.

    Google Scholar 

  71. Hagen FK, Nehrke K (1998) J Biol Chem 273: 8268–77.

    Google Scholar 

  72. Hilkens J, Buijs F (1988) J Biol Chem 263: 4215–22.

    Google Scholar 

  73. Dekker J, Van Beurden-Lamers WMO, Strous GJ (1989) J Biol Chem 264: 10431–37.

    Google Scholar 

  74. Hull SR, Sugarman ED, Spielman J, Carraway KL (1991) J Biol Chem 266: 13580–86.

    Google Scholar 

  75. McCool DJ, Forstner JF, Forstner GG (1994) Biochem J 302: 111–18.

    Google Scholar 

  76. Delorme, Lorenzini T, Griffin J, Martin F, Jacobsen F, Boone T, Elliott S (1992) Biochemistry 31: 9871–76.

    Google Scholar 

  77. Elliott S, Bartley T, Delorme E, Derby P, Hunt R, Lorenzini T, Parker V, Rohde MF, Stoney K (1994) Biochemistry 33: 11237–45.

    Google Scholar 

  78. Callaghan Rose M, Voter WA, Sage H, Brown CF, Kaufman B (1984) J Biol Chem 259: 3167–72.

    Google Scholar 

  79. Hounsell EF, Davies MJ, Renouf DV (1996) Glycoconj J 13: 19–26.

    Google Scholar 

  80. Brockhausen I (1993) Crit Rev Clin Lab Sci 30: 65–151.

    Google Scholar 

  81. Springer GF (1984) Science 224: 1198–206.

    Google Scholar 

  82. Takahashi HK, Metoki R, Hakamori S (1988) Cancer Res 48: 4361–67.

    Google Scholar 

  83. Gendler, SJ, Lancaster CA, Taylor-Papadimitriou J, Duhig T, Peat N, Burchell J, Pemberton L, Lalani E-N, Wilson D (1990) J Biol Chem 265: 15286–93.

    Google Scholar 

  84. Devine PL, McKenzie FC (1992) BioEssays 14: 619–25.

    Google Scholar 

  85. van de Wiel-van de Kemenade E, Ligtenberg MJL, de Boer AJ, Buijs F, Vos HL, Melief CJM, Hilkens J, Figdor CG (1993) J Immunol 151: 767–76.

    Google Scholar 

  86. Verma M, Davidson EA (1994) Glycoconj J 11: 172–79.

    Google Scholar 

  87. Hilkens J, Wesseling J, Vos HL, Litvinov SL, Boer M, van der Valk S, Calafat J, Patriarca C, van derWiel-van der Kemenade E, Figdor C (1995) In Biochemistry of Cell Membranes (Papa S, Tager JM, eds) pp 259–71. Basel/Switzerland: Birkhäuser Verlag.

    Google Scholar 

  88. Gimmi CD, Morrison BW, Mainpric BA, Gribben JG, Boussiotis VA, Freeman GJ, Park SYL, Wanatabe M, Gong JL, Hayes DF, Kufe DW, Nadler LM (1966) Nature Med 2: 1367–70

    Google Scholar 

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  1. Akira Kurosaka

    Present address: Pharmacia & Upjohn, 301 Henrietta, St, Kalamazoo, MI, 49007

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  1. Pharmacia & Upjohn, 301 Henrietta, St, Kalamazoo, MI, 49007

    Åke P. Elhammer & Ferenc J Kézdy

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  1. Åke P. Elhammer
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Elhammer, Å.P., Kézdy, F.J. & Kurosaka, A. The acceptor specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases. Glycoconj J 16, 171–180 (1999). https://doi.org/10.1023/A:1026465232149

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