Document Detail


Two dermatan sulfate epimerases form iduronic acid domains in dermatan sulfate.
MedLine Citation:
PMID:  19188366     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 amino acids long and has an approximately 700-amino acid 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 a short interfering RNA 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.
Authors:
Benny Pacheco; Anders Malmström; Marco Maccarana
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-06     Completed Date:  2009-05-20     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9788-95     Citation Subset:  IM    
Affiliation:
Department of Experimental Medical Science, Biomedical Center D12, Lund University, Tornavägen 10, SE-221 84 Lund, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Cell Line
Cells, Cultured
Dermatan Sulfate / chemistry*
Fibroblasts / metabolism
Glucuronic Acid / chemistry
Golgi Apparatus / metabolism
Humans
Iduronic Acid / chemistry*
Molecular Sequence Data
Plasmids / metabolism
Protein Structure, Tertiary
RNA, Small Interfering / metabolism
Racemases and Epimerases / metabolism*
Sulfotransferases / metabolism
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; 24967-94-0/Dermatan Sulfate; 3402-98-0/Iduronic Acid; 576-37-4/Glucuronic Acid; EC 2.8.2.-/Sulfotransferases; EC 5.1.-/Racemases and Epimerases
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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