title: A synthetic heparan sulfate oligosaccharide library reveals the novel enzymatic action of D-glucosaminyl 3-O-sulfotransferase-3a.
abstract: Heparan sulfate (HS) glucosaminyl 3-O-sulfotranferases sulfate the C3-hydroxyl group of certain glucosamine residues on heparan sulfate. Six different 3-OST isoforms exist, each of which can sulfate very distinct glucosamine residues within the HS chain. Among these isoforms, 3-OST1 has been shown to play a role in generating ATIII-binding HS anticoagulants whereas 3-OST2, 3-OST3, 3-OST4 and 3OST-6 have been shown to play a vital role in generating gD-binding HS chains that permit the entry of herpes simplex virus type 1 into cells. 3-OST5 has been found to generate both ATIII- and gD-binding HS motifs. Previous studies have examined the substrate specificities of all the 3-OST isoforms using HS polysaccharides. However, very few studies have examined the contribution of the epimer configuration of neighboring uronic acid residues next to the target site to 3-OST action. In this study, we utilized a well-defined synthetic oligosaccharide library to examine the substrate specificity of 3-OST3a and compared it to 3-OST1. We found that both 3-OST1 and 3-OST3a preferentially sulfate the 6-O-sulfated, N-sulfoglucosamine when an adjacent iduronyl residue is located to its reducing side. On the other hand, 2-O-sulfation of this uronyl residue can inhibit the action of 3-OST3a on the target residue. The results reveal novel substrate sites for the enzyme actions of 3-OST3a. It is also evident that both these enzymes have promiscuous and overlapping actions that are differentially regulated by iduronyl 2-O-sulfation.
authors: Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.
authors: Thao Kim Nu
authors: TK
authors: Nguyen
authors: Sailaja
authors: S
authors: Arungundram
authors: Vy My
authors: VM
authors: Tran
authors: Karthik
authors: K
authors: Raman
authors: Kanar
authors: K
authors: Al-Mafraji
authors: Andre
authors: A
authors: Venot
authors: Geert-Jan
authors: GJ
authors: Boons
authors: Balagurunathan
authors: B
authors: Kuberan
mesh_terms: D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D054852:Small Molecule Libraries; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D006497:Heparan Sulfate; D007527:Isoenzymes; D009844:Oligosaccharides; D054852:Small Molecule Libraries; D015238:Sulfotransferases; C093554:heparin-glucosamine 3-O-sulfotransferase