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Two dermatan sulfate epimerases form iduronic acid domains in dermatan sulfate.

Pacheco, Benny LU ; Malmström, Anders LU and Maccarana, Marco LU (2009) In Journal of Biological Chemistry 284. p.9788-9795
Abstract
A second dermatan sulfate epimerase (DS-epi2) was identified as a homolog of the first epimerase (DS-epi1), which was previously described by our group. DS-epi2 is 1,222 a.a. long and has a ~700-a.a. N-terminal epimerase domain that is highly conserved between the two enzymes. In addition, the C-terminal portion is predicted to be an O-sulfotransferase domain. In this study we found that DS-epi2 has epimerase activity, which involves conversion of D-glucuronic acid to L-iduronic acid (EC 5.1.3.19), but no O-sulfotransferase activity was detected. In dermatan sulfate, iduronic acid residues are either clustered together in blocks or alternating with glucuronic acid, forming hybrid structures. By using an siRNA approach, we found that... (More)
A second dermatan sulfate epimerase (DS-epi2) was identified as a homolog of the first epimerase (DS-epi1), which was previously described by our group. DS-epi2 is 1,222 a.a. long and has a ~700-a.a. N-terminal epimerase domain that is highly conserved between the two enzymes. In addition, the C-terminal portion is predicted to be an O-sulfotransferase domain. In this study we found that DS-epi2 has epimerase activity, which involves conversion of D-glucuronic acid to L-iduronic acid (EC 5.1.3.19), but no O-sulfotransferase activity was detected. In dermatan sulfate, iduronic acid residues are either clustered together in blocks or alternating with glucuronic acid, forming hybrid structures. By using an siRNA approach, we found that DS-epi2 and DS-epi1 are both involved in the biosynthesis of the iduronic acid blocks in fibroblasts and that DS-epi2 can also synthesize the hybrid structures. Both iduronic acid-containing domains have been shown to bind to several growth factors, many of which have biological roles in brain development. DS-epi2 has been genetically linked to bipolar disorder, which suggests that the dermatan sulfate domains generated by a defective enzyme may be involved in the etiology of the disease. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
284
pages
9788 - 9795
publisher
ASBMB
external identifiers
  • wos:000264892900019
  • pmid:19188366
  • scopus:65649100839
ISSN
1083-351X
DOI
10.1074/jbc.M809339200
language
English
LU publication?
yes
id
1096a767-ae94-4503-a1e0-5a304e7dbcaf (old id 1302957)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19188366?dopt=Abstract
date added to LUP
2009-03-02 14:38:18
date last changed
2017-11-26 03:51:33
@article{1096a767-ae94-4503-a1e0-5a304e7dbcaf,
  abstract     = {A second dermatan sulfate epimerase (DS-epi2) was identified as a homolog of the first epimerase (DS-epi1), which was previously described by our group. DS-epi2 is 1,222 a.a. long and has a ~700-a.a. N-terminal epimerase domain that is highly conserved between the two enzymes. In addition, the C-terminal portion is predicted to be an O-sulfotransferase domain. In this study we found that DS-epi2 has epimerase activity, which involves conversion of D-glucuronic acid to L-iduronic acid (EC 5.1.3.19), but no O-sulfotransferase activity was detected. In dermatan sulfate, iduronic acid residues are either clustered together in blocks or alternating with glucuronic acid, forming hybrid structures. By using an siRNA approach, we found that DS-epi2 and DS-epi1 are both involved in the biosynthesis of the iduronic acid blocks in fibroblasts and that DS-epi2 can also synthesize the hybrid structures. Both iduronic acid-containing domains have been shown to bind to several growth factors, many of which have biological roles in brain development. DS-epi2 has been genetically linked to bipolar disorder, which suggests that the dermatan sulfate domains generated by a defective enzyme may be involved in the etiology of the disease.},
  author       = {Pacheco, Benny and Malmström, Anders and Maccarana, Marco},
  issn         = {1083-351X},
  language     = {eng},
  pages        = {9788--9795},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Two dermatan sulfate epimerases form iduronic acid domains in dermatan sulfate.},
  url          = {http://dx.doi.org/10.1074/jbc.M809339200},
  volume       = {284},
  year         = {2009},
}