title: Uncovering biphasic catalytic mode of C5-epimerase in heparan sulfate biosynthesis.
abstract: Heparan sulfate (HS), a highly sulfated polysaccharide, is biosynthesized through a pathway involving several enzymes. C(5)-epimerase (C(5)-epi) is a key enzyme in this pathway. C(5)-epi is known for being a two-way catalytic enzyme, displaying a "reversible" catalytic mode by converting a glucuronic acid to an iduronic acid residue, and vice versa. Here, we discovered that C(5)-epi can also serve as a one-way catalyst to convert a glucuronic acid to an iduronic acid residue, displaying an "irreversible" catalytic mode. Our data indicated that the reversible or irreversible catalytic mode strictly depends on the saccharide substrate structures. The biphasic mode of C(5)-epi offers a novel mechanism to regulate the biosynthesis of HS with the desired biological functions.
authors.affiliation: Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
authors.forename: Juzheng
authors.initials: J
authors.lastname: Sheng
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xu
authors.forename: Steven B
authors.initials: SB
authors.lastname: Dulaney
authors.forename: Xuefei
authors.initials: X
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D002238:Carbohydrate Epimerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D020723:Glucuronic Acid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007067:Iduronic Acid / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D002238:Carbohydrate Epimerases; D020723:Glucuronic Acid; D006497:Heparan Sulfate; D007067:Iduronic Acid; D011994:Recombinant Proteins