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

Summary, in English

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: Benny Pacheco; Anders Malmström; Marco Maccarana
• Department/s: Matrix Biology
• Publishing year: 2009
• Language: English
• Pages: 9788-9795
• Publication/Series: Journal of Biological Chemistry
• Volume: 284
• Links: http://www.ncbi.nlm.nih.gov/pubmed/19188366?dopt=Abstract; http://dx.doi.org/10.1074/jbc.M809339200
• Document type: Journal article
• Publisher: American Society for Biochemistry and Molecular Biology
• Topic: Cell and Molecular Biology
• Status: Published
• Research group: Matrix Biology
• ISBN/ISSN/Other: ISSN: 1083-351X