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ProcessingO-glycan core 1, Galβ1-3GalNAcα-R. Specificities of core 2, UDP-GlcNAc: Galβ1-3GalNAc-R(GlcNAc to GalNAc) β6-N-acetylglucosaminyltransferase and CMP-sialic acid:Galβ1-3GalNAc-R α3-sialyltransferase

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Abstract

To elucidate control mechanisms ofO-glycan biosynthesis in leukemia and to develop biosynthetic inhibitors we have characterized core 2 UDP-GlcNAc:Galβ1-3GalNAc-R(GlcNAc to GalNAc) β6-N-acetylglucosaminyl-transferase (EC 2.4.1.102; core 2 β6-GlcNAc-T) and CMP-sialic acid: Galβ1-3GalNAc-R α3-sialyltransferase (EC 2.4.99.4; α3-SA-T), two enzymes that are significantly increased in patients with chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML). We observed distinct tissue-specific kinetic differences for the core 2 β6-GlcNAc-T activity; core 2 β6-GlcNAc-T from mucin secreting tissue (named core 2 β6-GlcNAc-T M) is accompanied by activities that synthesize core 4 [GlcNAcβ1-6(GlcNAcβ1-3)GalNAc-R] and blood group I [GlcNAcβ1-6(GlcNAcβ1-3)Galβ-R] branches; core 2 β6-GlcNAc-T in leukemic cells (named core 2 β-GlcNAc-T L) is not accompanied by these two activities and has a more restricted specificity. Core 2 β6-GlcNAc-T M and L both have an absolute requirement for the 4- and 6-hydroxyls ofN-acetylgalactosamine and the 6-hydroxyl of galactose of the Galβ1-3GalNAcα-benzyl substrate but the recognition of other substituents of the sugar rings varies, depending on the tissue. α3-sialytransferase from human placenta and from AML cells also showed distinct specificity differences, although the enzymes from both tissues have an absolute requirement for the 3-hydroxyl of the galactose residue of Galβ1-3GalNAcα-Bn. Galβ1-3(6-deoxy)GalNAcα-Bn and 3-deoxy-Galβ1-3GalNAcα-Bn competitively inhibited core 2 β6-GlcNAc-T and α3-sialyltransferase activities, respectively.

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Abbreviations

AFGP:

antifreeze glycoprotein

AML:

acute myeloid leukemia

Bn:

benzyl

CML:

chronic myelogenous leukemia

Fuc:

l-fucose

Gal, G:

d-galactose

GalNAc, GA:

N-acetyl-d-galactosamine

GlcNAc, Gn:

N-acetyl-d-glucosamine

HC:

human colonic homogenate

HO:

hen oviduct microsomes

HPLC:

high performance liquid chromatography

mco:

8-methoxycarbonyl-octy

Me:

methyl

MES:

2-(N-morpholino)ethanesulfonate

MK:

mouse kidney homogenate

onp:

o-nitrophenyl

PG:

pig gastric mucosal microsomes

pnp:

p-nitrophenyl

RC:

rat colonic mucosal microsomes

SA:

sialic acid

T:

transferase

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Authors and Affiliations

  1. Research Institute, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Ontario, Canada

    William Kuhns, Marijke Barner, Maria Granovsky & Inka Brockhausen

  2. Institut für Organische Chemie, Universität Hamburg, 2 Hamburg 13, Germany

    Volker Rutz & Hans Paulsen

  3. Department of Gynecologic Oncology, Roswell Park Memorial Institute, New York State Department of Health, 666 Elm Street, 14263, Buffalo, NY, USA

    Khushi L. Matta

  4. Department of Medicine, The Toronto Hospital and University of Toronto, M5G 1L7, Toronto, Ontario, Canada

    Michael A. Baker

  5. Department of Biochemistry, University of Toronto, M5S 1A8, Toronto, Ontario, Canada

    Maria Granovsky & Inka Brockhausen

Authors
  1. William Kuhns
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  2. Volker Rutz
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  3. Hans Paulsen
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  4. Khushi L. Matta
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  5. Michael A. Baker
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  6. Marijke Barner
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  7. Maria Granovsky
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  8. Inka Brockhausen
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Additional information

Enzymes: UDP-GlcNAc:Galβ1-3GalNAc-R (GlcNAc to GalNAc) β6-N-acetylglucosaminyltransferase,O-glycan core 2 β6-GlcNAc-transferase, EC 2.4.1.102; CMP-sialic acid: Galβ1-3GalNAc-R α3-sialyltransferase,O-glycan α3-sialic acid-transferase, EC 2.4.99.4.

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Kuhns, W., Rutz, V., Paulsen, H. et al. ProcessingO-glycan core 1, Galβ1-3GalNAcα-R. Specificities of core 2, UDP-GlcNAc: Galβ1-3GalNAc-R(GlcNAc to GalNAc) β6-N-acetylglucosaminyltransferase and CMP-sialic acid:Galβ1-3GalNAc-R α3-sialyltransferase. Glycoconjugate J 10, 381–394 (1993). https://doi.org/10.1007/BF00731043

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  • DOI: https://doi.org/10.1007/BF00731043

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