| Two dermatan sulfate epimerases form iduronic acid domains in dermatan sulfate. | |
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MedLine Citation:
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PMID: 19188366 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Benny Pacheco; Anders Malmström; Marco Maccarana |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-02-02 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-04-06 Completed Date: 2009-05-20 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 9788-95 Citation Subset: IM |
Affiliation:
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Department of Experimental Medical Science, Biomedical Center D12, Lund University, Tornavägen 10, SE-221 84 Lund, Sweden. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
| Comments/Corrections | |
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