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  • Zhang, TianjiNatl Inst Metrol, Div Chem & Analyt Sci, Beijing, Peoples R China.;Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing, Peoples R China.;Key Lab Chem Metrol & Applicat Nutr & Hlth State M, Beijing, Peoples R China. (author)

Interacting polymer-modification enzymes in heparan sulfate biosynthesis

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-488350
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-488350URI
  • https://doi.org/10.1016/j.carbpol.2022.120191DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Glucuronyl 5-epimerase (Hsepi) converts D-glucuronic acid (GlcA) into L-iduronic acid (IdoA) units, through a mechanism involving reversible abstraction of a proton at C5 of hexuronic acid residues. Incubations of a [4GlcA beta 1-4GlcNSO3 alpha 1-]n precursor substrate with recombinant enzymes in a D2O/H2O medium enabled an isotope exchange approach to the assessment of functional interactions of Hsepi with hexuronyl 2-O-sulfotrans-ferase (Hs2st) and glucosaminyl 6-O-sulfotransferase (Hs6st), both involved in the final polymer-modification steps. Enzyme complexes were supported by computational modeling and homogeneous time resolved fluores-cence. GlcA and IdoA D/H ratios related to product composition revealed kinetic isotope effects that were interpreted in terms of efficiency of the coupled epimerase and sulfotransferase reactions. Evidence for a func-tional Hsepi/Hs6st complex was provided by selective incorporation of D atoms into GlcA units adjacent to 6-O -sulfated glucosamine residues. The inability to achieve simultaneous 2-O-and 6-O-sulfation in vitro supported topologically separated reactions in the cell. These findings provide novel insight into the roles of enzyme in-teractions in heparan sulfate biosynthesis.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Yu, MingjiaBeijing Inst Technol, Sch Chem & Chem Engn, Beijing, Peoples R China.;Beijing Univ Chem Technol, Beijing Adv Innovat Ctr Soft Matter Sci & Engn, Beijing, Peoples R China. (author)
  • Li, HonglianUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)honli111 (author)
  • Maccarana, MarcoUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)marma713 (author)
  • Zhang, WeiNatl Inst Metrol, Div Chem & Analyt Sci, Beijing, Peoples R China. (author)
  • Shi, DelingShandong Univ, Natl Glycoengn Res Ctr, Jinan, Peoples R China. (author)
  • Kan, YingNatl Inst Metrol, Div Chem & Analyt Sci, Beijing, Peoples R China.;Key Lab Chem Metrol & Applicat Nutr & Hlth State M, Beijing, Peoples R China. (author)
  • Zhang, XiaoUppsala universitet,Forskargrupp Dan Larhammar(Swepub:uu)xizha255 (author)
  • Chi, LianliShandong Univ, Natl Glycoengn Res Ctr, Jinan, Peoples R China. (author)
  • Lindahl, UlfUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)uli08750 (author)
  • Li, HongmeiNatl Inst Metrol, Div Chem & Analyt Sci, Beijing, Peoples R China.;Key Lab Chem Metrol & Applicat Nutr & Hlth State M, Beijing, Peoples R China. (author)
  • Li, Jin-PingUppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Beijing Univ Chem Technol, Beijing Adv Innovat Ctr Soft Matter Sci & Engn, Beijing, Peoples R China.(Swepub:uu)jinpili (author)
  • Tan, TianweiBeijing Univ Chem Technol, Coll Life Sci & Technol, Beijing, Peoples R China. (author)
  • Natl Inst Metrol, Div Chem & Analyt Sci, Beijing, Peoples R China.;Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing, Peoples R China.;Key Lab Chem Metrol & Applicat Nutr & Hlth State M, Beijing, Peoples R China.Beijing Inst Technol, Sch Chem & Chem Engn, Beijing, Peoples R China.;Beijing Univ Chem Technol, Beijing Adv Innovat Ctr Soft Matter Sci & Engn, Beijing, Peoples R China. (creator_code:org_t)

Related titles

  • In:Carbohydrate Polymers: Elsevier2990144-86171879-1344

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