Evidence map›Paper›PMID 40163365›Full record

ArticleeLife2025

Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody.

Joar Esteban Pinto Torres, Mathieu Claes, Rik Hendrickx, Meng Yuan, Natalia Smiejkowska, Pieter Van Wielendaele, Aysima Hacisuleyman, Hans De Winter, Serge Muyldermans, Paul A M Michels and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Nanobodies in animal infectious disease control: diagnosis and therapy.Frontiers in cellular and infection microbiology · 2025
    Review
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

15 authors.

Joar Esteban Pinto TorresLaboratory for Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel (VUB), Brussel, Belgium.
Mathieu ClaesLaboratory of Microbiology, Parasitology and Hygiene (LMPH) and the Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.
Rik HendrickxLaboratory of Microbiology, Parasitology and Hygiene (LMPH) and the Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.
Meng Yuan *School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
Natalia SmiejkowskaLaboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.
Pieter Van WielendaeleLaboratory of Medical Biochemistry (LMB) and the Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.
Aysima HacisuleymanDepartment of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Hans De WinterLaboratory of Medicinal Chemistry, University of Antwerp, Wilrijk, Belgium.
Serge MuyldermansLaboratory for Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel (VUB), Brussel, Belgium.
Paul A M MichelsSchool of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
Malcolm D WalkinshawSchool of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
Wim VerséesVIB-VUB Center for Structural Biology, VIB, Brussels, Belgium.ORCID https://orcid.org/0000-0002-4695-696X
Guy CaljonLaboratory of Microbiology, Parasitology and Hygiene (LMPH) and the Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.ORCID https://orcid.org/0000-0002-4870-3202
Stefan Magez *Laboratory for Cellular and Molecular Immunology (CMIM), Vrije Universiteit Brussel (VUB), Brussel, Belgium.
Yann G-J Sterckx *Laboratory of Microbiology, Parasitology and Hygiene (LMPH) and the Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.ORCID https://orcid.org/0000-0002-7420-0983

Funding

COST Action CA21111 CA21111Fonds Wetenschappelijk Onderzoek 1137622NFonds Wetenschappelijk Onderzoek G013518NUniversiteit Antwerpen 41391Universiteit Gent BOF.STG.2018.0009.01/01N01518Vrije Universiteit Brussel SRP95
6 · The paper itself

Abstract

African trypanosomes are the causative agents of neglected tropical diseases affecting both humans and livestock. Disease control is highly challenging due to an increasing number of drug treatment failures. African trypanosomes are extracellular, blood-borne parasites that mainly rely on glycolysis for their energy metabolism within the mammalian host. Trypanosomal glycolytic enzymes are therefore of interest for the development of trypanocidal drugs. Here, we report the serendipitous discovery of a camelid single-domain antibody (sdAb aka Nanobody) that selectively inhibits the enzymatic activity of trypanosomatid (but not host) pyruvate kinases through an allosteric mechanism. By combining enzyme kinetics, biophysics, structural biology, and transgenic parasite survival assays, we provide a proof-of-principle that the sdAb-mediated enzyme inhibition negatively impacts parasite fitness and growth.

Indexed as

Pyruvate KinaseSingle-Domain AntibodiesTrypanosoma brucei bruceiAllosteric RegulationAnimalsCamelidaeKineticsProtozoan ProteinsProtozoan ProteinsPyruvate KinaseSingle-Domain Antibodiesallosteric inhibitionbiochemistrycamelid single-domain antibodychemical biologyE. coli bl21(de3)molecular biophysicspyruvate kinasestructural biologyT. brucei lister 427 single-marker (tb427sm)Trypanosoma brucei

Identifiers

PMID40163365
PMCPMC11957543

What OpenQuestion holds

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Registered trials

None linked

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.