Discovery - University of Dundee - Online Publications

Library & Learning Centre

Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity

Standard

Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity. / Gulberti, Sandrine; Jacquinet, Jean-Claude; Chabel, Matthieu; Ramalanjaona, Nick; Magdalou, Jacques; Netter, Patrick; Coughtrie, Michael W. H.; Ouzzine, Mohamed; Fournel-Gigleux, Sylvie.

In: Glycobiology, Vol. 22, No. 4, 04.2012, p. 561-571.

Research output: Contribution to journalArticle

Harvard

Gulberti, S, Jacquinet, J-C, Chabel, M, Ramalanjaona, N, Magdalou, J, Netter, P, Coughtrie, MWH, Ouzzine, M & Fournel-Gigleux, S 2012, 'Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity' Glycobiology, vol 22, no. 4, pp. 561-571.

APA

Gulberti, S., Jacquinet, J-C., Chabel, M., Ramalanjaona, N., Magdalou, J., Netter, P., Coughtrie, M. W. H., Ouzzine, M., & Fournel-Gigleux, S. (2012). Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity. Glycobiology, 22(4), 561-571doi: 10.1093/glycob/cwr172

Vancouver

Gulberti S, Jacquinet J-C, Chabel M, Ramalanjaona N, Magdalou J, Netter P et al. Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity. Glycobiology. 2012 Apr;22(4):561-571.

Author

Gulberti, Sandrine; Jacquinet, Jean-Claude; Chabel, Matthieu; Ramalanjaona, Nick; Magdalou, Jacques; Netter, Patrick; Coughtrie, Michael W. H.; Ouzzine, Mohamed; Fournel-Gigleux, Sylvie / Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity.

In: Glycobiology, Vol. 22, No. 4, 04.2012, p. 561-571.

Research output: Contribution to journalArticle

Bibtex - Download

@article{45041f499be3406193d36c3102f412d4,
title = "Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity",
author = "Sandrine Gulberti and Jean-Claude Jacquinet and Matthieu Chabel and Nick Ramalanjaona and Jacques Magdalou and Patrick Netter and Coughtrie, {Michael W. H.} and Mohamed Ouzzine and Sylvie Fournel-Gigleux",
year = "2012",
volume = "22",
number = "4",
pages = "561--571",
journal = "Glycobiology",
issn = "0959-6658",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1) involved in chondroitin sulfate initiation: Impact of sulfation on activity and specificity

A1 - Gulberti,Sandrine

A1 - Jacquinet,Jean-Claude

A1 - Chabel,Matthieu

A1 - Ramalanjaona,Nick

A1 - Magdalou,Jacques

A1 - Netter,Patrick

A1 - Coughtrie,Michael W. H.

A1 - Ouzzine,Mohamed

A1 - Fournel-Gigleux,Sylvie

AU - Gulberti,Sandrine

AU - Jacquinet,Jean-Claude

AU - Chabel,Matthieu

AU - Ramalanjaona,Nick

AU - Magdalou,Jacques

AU - Netter,Patrick

AU - Coughtrie,Michael W. H.

AU - Ouzzine,Mohamed

AU - Fournel-Gigleux,Sylvie

PY - 2012/4

Y1 - 2012/4

N2 - <p>Glycosaminoglycan (GAG) assembly initiates through the formation of a linkage tetrasaccharide region serving as a primer for both chondroitin sulfate (CS) and heparan sulfate (HS) chain polymerization. A possible role for sulfation of the linkage structure and of the constitutive disaccharide unit of CS chains in the regulation of CS-GAG chain synthesis has been suggested. To investigate this, we determined whether sulfate substitution of galactose (Gal) residues of the linkage region or of N-acetylgalactosamine (GalNAc) of the disaccharide unit influences activity and specificity of chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1), a key glycosyltransferase of CS biosynthesis. We synthesized a series of sulfated and unsulfated analogs of the linkage oligosaccharide and of the constitutive unit of CS and tested these molecules as potential acceptor substrates for the recombinant human CSGalNAcT-1. We show here that sulfation at C4 or C6 of the Gal residues markedly influences CSGalNAcT-1 initiation activity and catalytic efficiency. Kinetic analysis indicates that CSGalNAcT-1 exhibited 3.6-, 1.6-, and 2.2-fold higher enzymatic efficiency due to lower K-m values toward monosulfated trisaccharides substituted at C4 or C6 position of Gal1, and at C6 of Gal2, respectively, compared with the unsulfated oligosaccharide. This highlights the critical influence of Gal substitution on both CSGalNAcT-1 activity and specifity. No GalNAcT activity was detected toward sulfated and unsulfated analogs of the CS constitutive disaccharide (GlcA-beta 1,3-GalNAc), indicating that CSGalNAcT-1 was involved in initiation but not in elongation of CS chains. Our results strongly suggest that sulfation of the linkage region acts as a regulatory signal in CS chain initiation.</p>

AB - <p>Glycosaminoglycan (GAG) assembly initiates through the formation of a linkage tetrasaccharide region serving as a primer for both chondroitin sulfate (CS) and heparan sulfate (HS) chain polymerization. A possible role for sulfation of the linkage structure and of the constitutive disaccharide unit of CS chains in the regulation of CS-GAG chain synthesis has been suggested. To investigate this, we determined whether sulfate substitution of galactose (Gal) residues of the linkage region or of N-acetylgalactosamine (GalNAc) of the disaccharide unit influences activity and specificity of chondroitin sulfate N-acetylgalactosaminyltransferase-1 (CSGalNAcT-1), a key glycosyltransferase of CS biosynthesis. We synthesized a series of sulfated and unsulfated analogs of the linkage oligosaccharide and of the constitutive unit of CS and tested these molecules as potential acceptor substrates for the recombinant human CSGalNAcT-1. We show here that sulfation at C4 or C6 of the Gal residues markedly influences CSGalNAcT-1 initiation activity and catalytic efficiency. Kinetic analysis indicates that CSGalNAcT-1 exhibited 3.6-, 1.6-, and 2.2-fold higher enzymatic efficiency due to lower K-m values toward monosulfated trisaccharides substituted at C4 or C6 position of Gal1, and at C6 of Gal2, respectively, compared with the unsulfated oligosaccharide. This highlights the critical influence of Gal substitution on both CSGalNAcT-1 activity and specifity. No GalNAcT activity was detected toward sulfated and unsulfated analogs of the CS constitutive disaccharide (GlcA-beta 1,3-GalNAc), indicating that CSGalNAcT-1 was involved in initiation but not in elongation of CS chains. Our results strongly suggest that sulfation of the linkage region acts as a regulatory signal in CS chain initiation.</p>

U2 - 10.1093/glycob/cwr172

DO - 10.1093/glycob/cwr172

M1 - Article

JO - Glycobiology

JF - Glycobiology

SN - 0959-6658

IS - 4

VL - 22

SP - 561

EP - 571

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy