Evidence map›Paper›PMID 42559965›Full record

ArticleAngewandte Chemie (International ed. in English)2026

Unraveling A4GALT Mechanism and Its Modulation With Adamantyl-Galactosylceramide Analogues: Advancing Fabry Disease Therapeutic Strategies.

Nicky de Koster, Òscar Vidal-Gironès, Rowan de Graaf, Ken Kok, Lindsey T Lelieveld, Jackelien Hoogervorst, Maria J Ferraz, José Pablo Rivas-Fernández, Rob F Lammers, Herman S Overkleeft and 4 more

Abstract read
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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. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Nicky de KosterDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-9291-5026
Òscar Vidal-GironèsDepartament De Química Inorgànica i Orgànica (Secció de Química Orgànica) and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Barcelona, Spain.ORCID https://orcid.org/0009-0009-7841-141X
Rowan de GraafDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.
Ken KokDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.
Lindsey T LelieveldDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.
Jackelien HoogervorstDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.
Maria J FerrazDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-5765-9645
José Pablo Rivas-FernándezDepartament De Química Inorgànica i Orgànica (Secció de Química Orgànica) and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Barcelona, Spain.ORCID https://orcid.org/0000-0002-1349-3049
Rob F LammersDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.ORCID https://orcid.org/0000-0001-7237-2303
Herman S OverkleeftDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.ORCID https://orcid.org/0000-0001-6976-7005
Johannes M F G AertsDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.ORCID https://orcid.org/0000-0001-8168-2565
Rolf G BootDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-7031-3390
Carme RoviraDepartament De Química Inorgànica i Orgànica (Secció de Química Orgànica) and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Barcelona, Spain.ORCID https://orcid.org/0000-0003-1477-5010
Marta ArtolaDepartment of Medical Biochemistry and Department of Bio-organic Synthesis, Leiden Institute of Chemistry (LIC), Leiden University, Leiden, the Netherlands.ORCID https://orcid.org/0000-0002-3051-3902

Funding

Agency for Management of University and Research Grants of Catalonia 2021-SGR-00680European Research Council ERC-2024-STG 101163762Spanish Ministry of Science, Innovation and Universities MICIU/AEI/10.13039/501100011033-PID2023-147939NB-I00Spanish Structures of Excellence María de Maeztu MICIU/AEI/10.13039/501100011033-CEX2021-001202-M
6 · The paper itself

Abstract

Fabry disease (FD), one of the most prevalent lysosomal storage disorders in Europe, is caused by mutations in the GLA gene leading to deficient α-galactosidase A activity with lysosomal accumulation of globotriaosylceramide (Gb3). Enzyme replacement therapy (ERT) and pharmacological chaperone therapy (PCT) are used in the clinic to treat FD but are limited in efficacy, underscoring the need for alternative therapeutic strategies. Inhibiting α-1,4-galactosyltransferase (A4GALT), the glycosyltransferase responsible for Gb3 biosynthesis, represents an attractive strategy. Here, we reveal the molecular mechanism of human A4GALT at atomic detail using QM/MM simulations. We reveal a conformational rearrangement involving a 3

Indexed as

Enzyme InhibitorsFabry DiseaseGalactosylceramidesGalactosyltransferasesHumansTrihexosylceramidesEnzyme InhibitorsGalactosylceramidesGalactosyltransferasesglobotriaosylceramideTrihexosylceramidesUDP-galactose-lactosylceramide alpha 1-4-galactosyltransferaseFabry diseaseGb3 synthase A4GALTglobotriaosylceramideglycosphingolipidsglycosyltransferase mechanismsubstrate reduction therapy

Identifiers

PMID42559965
PMCPMC13638101

What OpenQuestion holds

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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.