Evidence map›Paper›PMID 42175780›Full record

ArticleFEBS letters2026

Crystal structure of Mycobacterium tuberculosis mycothione reductase in complex with a specific inhibitor reveals competition with NADP(H) binding.

Lauren Oorts, Evgenii M Osipov, Steven Beelen, Natalia Smiejkowska, Kevin Van Calster, Dirk Lamprecht, Koen Temmerman, Arthur Van Aerschot, Davie Cappoen, Paul Cos and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FEBS letters, 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

11 authors.

Lauren OortsLaboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Evgenii M OsipovBiocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Steven BeelenBiocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Natalia SmiejkowskaLaboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Kevin Van CalsterLaboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Dirk LamprechtJanssen Pharmaceutica NV, Beerse, Belgium.
Koen TemmermanJanssen Pharmaceutica NV, Beerse, Belgium.
Arthur Van AerschotBiocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Davie CappoenLaboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Paul CosLaboratory of Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
Sergei V StrelkovBiocrystallography, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.ORCID https://orcid.org/0000-0001-7189-4652

Funding

Fonds Wetenschappelijk Onderzoek G066619NFonds Wetenschappelijk Onderzoek I007220NInnovative Health Initiative 853903
6 · The paper itself

Abstract

Tuberculosis (TB) remains a major health threat, while the increasing occurrence of drug-resistant strains underscores the need for new antitubercular drugs. A promising strategy to combat TB is based on disrupting the mycobacterial redox homeostasis by inhibiting an NADPH-dependent oxidoreductase, mycothione reductase (Mtr). Using high-throughput screening, we recently identified potent and selective Mtr inhibitors. Here we report high-resolution X-ray structures of Mtr from Mycobacterium tuberculosis and Mycobacterium xenopi, including the M. tuberculosis enzyme complexed with a novel inhibitor, Respiri-1093. Our findings demonstrate that Respiri-1093 competes with the NADP(H) binding rather than mycothione binding. Analysis of the binding site explains the observed selectivity of the inhibitor towards the M. tuberculosis enzyme. These results provide a structural basis for rational drug design.

Indexed as

Antitubercular AgentsBacterial ProteinsEnzyme InhibitorsMycobacterium tuberculosisNADPBinding, CompetitiveBinding SitesCrystallography, X-RayModels, MolecularProtein BindingProtein ConformationAntitubercular AgentsBacterial ProteinsEnzyme InhibitorsNADPcrystal structuredrug designMycobacterium tuberculosismycothione reductaseNADPHsmall‐molecule inhibitor

Identifiers

PMID42175780
PMCPMC13456609

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.