title: Engineering sulfotransferases to modify heparan sulfate.
abstract: The biosynthesis of heparan sulfate (HS) involves an array of specialized sulfotransferases. Here, we present a study aimed at engineering the substrate specificity of different HS 3-O-sulfotransferase isoforms. Based on the crystal structures, we identified a pair of amino acid residues responsible for selecting the substrates. Mutations of these residues altered the substrate specificities. Our results demonstrate the feasibility of tailoring the specificity of sulfotransferases to modify HS with desired functions.
authors.affiliation: Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Ding
authors.initials: D
authors.lastname: Xu
authors.forename: Andrea F
authors.initials: AF
authors.lastname: Moon
authors.forename: Danyin
authors.initials: D
authors.lastname: Song
authors.forename: Lars C
authors.initials: LC
authors.lastname: Pedersen
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D001665:Binding Sites; D002236:Carbohydrate Conformation; D005240:Feasibility Studies; D006497:Heparan Sulfate / Q000096:biosynthesis* / Q000737:chemistry; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D015202:Protein Engineering; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D006497:Heparan Sulfate; D020033:Protein Isoforms; D015238:Sulfotransferases; C102180:heparan sulfate D-glucosaminyl 3-O-sulfotransferase