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(AMNE:(MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology)) pers:(Malmström Anders)
 

Search: (AMNE:(MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology)) pers:(Malmström Anders) > The structure of hu...

  • Hasan, MahmudulLund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH (author)

The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021
  • Royal Society of Chemistry (RSC),2021
  • 17 s.

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:7f5e95b2-2227-428e-9353-e25b4e07f4f0
  • https://lup.lub.lu.se/record/7f5e95b2-2227-428e-9353-e25b4e07f4f0URI
  • https://doi.org/10.1039/d0sc05971dDOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Dermatan sulfate epimerase 1 (DS-epi1, EC 5.1.3.19) catalyzes the conversion of d-glucuronic acid to l-iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS-epi1, solved at 2.4 Å resolution, as well as a model of the full-length luminal protein obtained by a combination of macromolecular crystallography and targeted cross-linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS-epi1, involving a His/double-Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal-coordinating center and pattern of N-glycosylation of the protein. Additionally, the structure of DS-epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS-epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitors.

Subject headings and genre

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

  • Khakzad, HamedÉcole normale supérieure Paris-Saclay (author)
  • Happonen, LottaLund University,Lunds universitet,Molekylär patogenes,Forskargrupper vid Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,BioMS,Molecular Pathogenesis,Lund University Research Groups,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research(Swepub:lu)immu-loh (author)
  • Sundin, AndersLund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Bioteknik,Centrum för tillämpade biovetenskaper,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,Biotechnology,Center for Applied Life Sciences,Faculty of Engineering, LTH(Swepub:lu)ok2-aps (author)
  • Unge, JohanUniversity of California, Los Angeles(Swepub:lu)mbfy-jun (author)
  • Mueller, UweHelmholtz Association of German Research Centers (author)
  • Malmström, JohanLund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,BioMS,Lund University Research Groups,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research(Swepub:lu)medk-jma (author)
  • Westergren-Thorsson, GunillaLund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,WCMM- Wallenberg center för molekylär medicinsk forskning,Lung Biology,Lund University Research Groups,Faculty of Medicine,WCMM-Wallenberg Centre for Molecular Medicine(Swepub:lu)medk-gwt (author)
  • Malmström, LarsLund University,Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,epIgG,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups(Swepub:lu)elma-lma (author)
  • Ellervik, UlfLund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Bioteknik,Centrum för tillämpade biovetenskaper,Lung Biology,Lund University Research Groups,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,Biotechnology,Center for Applied Life Sciences,Faculty of Engineering, LTH(Swepub:lu)ok2-uel (author)
  • Malmström, AndersLund University,Lunds universitet,Matrixbiologi,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Matrix Biology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine(Swepub:lu)medk-ama (author)
  • Tykesson, EmilLund University,Lunds universitet,Matrixbiologi,Forskargrupper vid Lunds universitet,Matrix Biology,Lund University Research Groups(Swepub:lu)med-elt (author)
  • Biokemi och StrukturbiologiCentrum för Molekylär Proteinvetenskap (creator_code:org_t)

Related titles

  • In:Chemical Science: Royal Society of Chemistry (RSC)12:5, s. 1869-18852041-65202041-6539

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