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URN to cite this document: urn:nbn:de:bvb:703-epub-9082-0
Title data
Weidler, Sascha ; Bundgaard, Klaus Ole ; Hessefort, Markus ; Rädisch, Marisa ; Graf, Christopher Günther Franz ; Lam, Kevin ; Neubauer, Vanessa J. ; Eisenreich, Johanna ; Köhler, Leonhard ; Moremen, Kelley W. ; Steentoft, Catharina ; Clausen, Henrik ; Huang, Teng-Yi ; Hung, Shang-Cheng ; Steegborn, Clemens ; Weyand, Michael ; Unverzagt, Carlo:
Human Proteoglycan Linkage Region Glycosyltransferases are Dimeric and Show Unexpected Specificities.
In: Angewandte Chemie International Edition.
Vol. 65
(2026)
Issue 3
.
- e16855.
ISSN 1521-3773
DOI der Verlagsversion: https://doi.org/10.1002/anie.202516855
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Project information
| Project title: |
Project's official title Project's id Semisynthesis of natural glycoforms of human erythropoietin 223435149 SPP 1623: Chemoselektive Reaktionen für die Synthese und Anwendung funktionaler Proteine 198742546 Open Access Publizieren No information |
|---|---|
| Project financing: |
Deutsche Forschungsgemeinschaft |
Abstract
We selected the N,O-glycosylated proteoglycan bikunin as a model to establish a chemoenzymatic approach to defined proteoglycans using native chemical ligation. Overexpression of the human linkage region glycosyltransferases B4GalT7, B3GalT6 and B3GlcAT-1 as N-terminal SUMO-fusions gave high yields of soluble and active enzymes in E. coli. When starting with xylosylated bikunin peptides the transferases performed well in enzymatic cascade reactions and provided the desired linkage region tetrasaccharide glycopeptides. B3GalT6 and B3GlcAT-1 led to side products with N,O-glycosylated bikunin peptides revealing unexpected promiscuity of both enzymes towards complex type N-glycans. Additionally, B3GalT6 was found to synthesize short poly-β3 Gal structures. B3GlcAT-1 can slowly convert the biosynthetic intermediate Gal-Xyl to the non-canonical trisaccharide GlcA-Gal-Xyl. This reaction independently confirmed the recently detected biosynthetic bypass to GAGs in the case of dysfunctional B3GalT6 (spondylodysplastic Ehlers-Danlos-syndrome). The three linkage region glycosyltransferases B4GalT7, B3GalT6 and B3GlcAT-1 were dimeric in solution and the crystal structure of B3GalT6 was solved showing a covalent dimer linked by a disulfide in the center of the large dimerization domain. This motif appears to be conserved in higher organisms and reinforces the concept of dimeric glycosyltransferases lining the Golgi.
Further data
| Item Type: | Article in a journal |
|---|---|
| Keywords: | Enzymes; Glycoconjugates; Glycopeptides; Protein structures; Proteoglycan |
| DDC Subjects: | 500 Science > 540 Chemistry |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Organic Chemistry II - Bioorganic Chemistry - Univ.-Prof. Dr. Carlo Unverzagt Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Biochemistry - Univ.-Prof. Dr. Clemens Steegborn Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors |
| Language: | English |
| Originates at UBT: | Yes |
| URN: | urn:nbn:de:bvb:703-epub-9082-0 |
| Date Deposited: | 07 Apr 2026 12:30 |
| Last Modified: | 07 Apr 2026 12:30 |
| URI: | https://epub.uni-bayreuth.de/id/eprint/9082 |
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