Dermatan 4-O-sulfotransferase 1 is pivotal in the formation of iduronic acid blocks in dermatan sulfate.
Pacheco, Benny LU ; Maccarana, Marco LU and Malmström, Anders LU
(2009)
In Glycobiology
19.
p.1197-1203
- Abstract
- Chondroitin/dermatan sulfate is a highly complex linear polysaccharide ubiquitously found in the extracellular matrix and at the cell surface. Several of its functions, such as binding to growth factors, are mediated by domains composed of alternating iduronic acid and 4-O-sulfated N-acetylgalactosamine residues, named 4-O-sulfated iduronic acid blocks. These domains are generated by the action of two DS-epimerases, which convert D-glucuronic acid into its epimer L-iduronic acid, in close connection with 4-O-sulfation. In this study, dermatan sulfate structure was evaluated after downregulating or increasing dermatan 4-O-sulfotransferase 1 (D4ST-1) expression. SiRNA-mediated downregulation of D4ST-1 in primary human lung fibroblasts led to... (More)
- Chondroitin/dermatan sulfate is a highly complex linear polysaccharide ubiquitously found in the extracellular matrix and at the cell surface. Several of its functions, such as binding to growth factors, are mediated by domains composed of alternating iduronic acid and 4-O-sulfated N-acetylgalactosamine residues, named 4-O-sulfated iduronic acid blocks. These domains are generated by the action of two DS-epimerases, which convert D-glucuronic acid into its epimer L-iduronic acid, in close connection with 4-O-sulfation. In this study, dermatan sulfate structure was evaluated after downregulating or increasing dermatan 4-O-sulfotransferase 1 (D4ST-1) expression. SiRNA-mediated downregulation of D4ST-1 in primary human lung fibroblasts led to a drastic specific reduction of iduronic acid blocks. No change of epimerase activity was found, indicating that the influence of D4ST-1 on epimerization is not due to an altered expression level of the DS-epimerases. Analysis of the dermatan sulfate chains showed that D4ST-1 is essential for the biosynthesis of the disulfated structure iduronic acid-2-O-sulfate-N-acetylgalactosamine-4-O-sulfate, thus confirmed to be strictly connected with the iduronic acid blocks. Also the biologically important residue hexuronic acid-N-acetylgalactosamine-4,6-O-disulfate considerably decreased after D4ST-1 downregulation. In conclusion, D4ST-1 is a key enzyme and is indispensable in the formation of important functional domains in dermatan sulfate and cannot be compensated by other 4-O-sulfotransferases. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1469927
- author
- Pacheco, Benny
LU
; Maccarana, Marco
LU
and Malmström, Anders
LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Glycobiology
- volume
- 19
- pages
- 1197 - 1203
- publisher
- Oxford University Press
- external identifiers
-
- wos:000270707700005
- pmid:19661164
- scopus:70349989501
- pmid:19661164
- ISSN
- 1460-2423
- DOI
- 10.1093/glycob/cwp110
- language
- English
- LU publication?
- yes
- id
- bd366d07-40c3-4354-9d88-582bf0bc9494 (old id 1469927)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19661164?dopt=Abstract
- date added to LUP
- 2016-04-04 09:13:34
- date last changed
- 2022-02-13 08:18:47
@article{bd366d07-40c3-4354-9d88-582bf0bc9494,
abstract = {{Chondroitin/dermatan sulfate is a highly complex linear polysaccharide ubiquitously found in the extracellular matrix and at the cell surface. Several of its functions, such as binding to growth factors, are mediated by domains composed of alternating iduronic acid and 4-O-sulfated N-acetylgalactosamine residues, named 4-O-sulfated iduronic acid blocks. These domains are generated by the action of two DS-epimerases, which convert D-glucuronic acid into its epimer L-iduronic acid, in close connection with 4-O-sulfation. In this study, dermatan sulfate structure was evaluated after downregulating or increasing dermatan 4-O-sulfotransferase 1 (D4ST-1) expression. SiRNA-mediated downregulation of D4ST-1 in primary human lung fibroblasts led to a drastic specific reduction of iduronic acid blocks. No change of epimerase activity was found, indicating that the influence of D4ST-1 on epimerization is not due to an altered expression level of the DS-epimerases. Analysis of the dermatan sulfate chains showed that D4ST-1 is essential for the biosynthesis of the disulfated structure iduronic acid-2-O-sulfate-N-acetylgalactosamine-4-O-sulfate, thus confirmed to be strictly connected with the iduronic acid blocks. Also the biologically important residue hexuronic acid-N-acetylgalactosamine-4,6-O-disulfate considerably decreased after D4ST-1 downregulation. In conclusion, D4ST-1 is a key enzyme and is indispensable in the formation of important functional domains in dermatan sulfate and cannot be compensated by other 4-O-sulfotransferases.}},
author = {{Pacheco, Benny and Maccarana, Marco and Malmström, Anders}},
issn = {{1460-2423}},
language = {{eng}},
pages = {{1197--1203}},
publisher = {{Oxford University Press}},
series = {{Glycobiology}},
title = {{Dermatan 4-O-sulfotransferase 1 is pivotal in the formation of iduronic acid blocks in dermatan sulfate.}},
url = {{http://dx.doi.org/10.1093/glycob/cwp110}},
doi = {{10.1093/glycob/cwp110}},
volume = {{19}},
year = {{2009}},
}