Evidence map›Paper›PMID 41316887›Full record

ArticleAngewandte Chemie (International ed. in English)2026

Human Proteoglycan Linkage Region Glycosyltransferases are Dimeric and Show Unexpected Specificities.

Sascha Weidler, Ole Bundgaard, Markus Hessefort, Marisa Rädisch, Christopher Günther Franz Graf, Kevin Lam, Vanessa J Neubauer, Johanna Eisenreich, Leonhard Köhler, Kelley W Moremen and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Sascha WeidlerUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Ole BundgaardUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Markus HessefortUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Marisa RädischUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Christopher Günther Franz GrafUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Kevin LamUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Vanessa J NeubauerUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Johanna EisenreichUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Leonhard KöhlerUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.
Kelley W MoremenComplex Carbohydrate Research Center, University of Georgia, Athens, GA, 30602, USA.
Catharina SteentoftCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and School of Dentistry, University of Copenhagen, Denmark.
Henrik ClausenCopenhagen Center for Glycomics, Departments of Cellular and Molecular Medicine and School of Dentistry, University of Copenhagen, Denmark.
Teng-Yi HuangGenomics Research Center, Academia Sinica, Taipei, Taiwan.
Shang-Cheng HungGenomics Research Center, Academia Sinica, Taipei, Taiwan.
Clemens SteegbornDepartment of Biochemistry, University of Bayreuth, 95447, Bayreuth, Germany.
Michael WeyandDepartment of Biochemistry, University of Bayreuth, 95447, Bayreuth, Germany.
Carlo UnverzagtUniversity of Bayreuth, Bioorganic Chemistry, Universitätsstraße 30, 95447, Bayreuth, Germany.ORCID 0000-0001-6492-1747

Funding

Deutsche ForschungsgemeinschaftNSF NSF 2400220
6 · The paper itself

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.

Indexed as

GlycosyltransferasesProteoglycansHumansProtein MultimerizationSubstrate SpecificityGlycosyltransferasesProteoglycansEnzymesGlycoconjugatesGlycopeptidesProtein structuresProteoglycan

Identifiers

PMID41316887
PMCPMC12811666

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.