Evidence map›Paper›PMID 42687039›Full record

ArticleNature chemical biology2026

Mechanism of the M. tuberculosis DprE1-DprE2 epimerase complex and inhibition by anti-tubercular drugs.

Shan Gao, Fangyu Wu, Yifan Zhang, Sarah M Batt, Chuancun Wei, Zeyu Wang, Xiuna Yang, Katherine A Abrahams, Klaus Fütterer, Xinliang Liu and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. The metabolic road from α-cells to β-cells.Nature chemical biology · 2026
    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

14 authors.

Shan Gao *Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0009-0002-2465-2903
Fangyu Wu *Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0000-0003-3799-6959
Yifan Zhang *Shanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Sarah M BattInstitute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0003-1955-2967
Chuancun WeiShanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0009-0008-1387-4950
Zeyu WangShanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Xiuna YangShanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0000-0003-3443-9815
Katherine A AbrahamsInstitute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK.ORCID http://orcid.org/0000-0002-0769-3423
Klaus FüttererInstitute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK.
Xinliang LiuSchool of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China.
Ping WangSchool of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, China.ORCID http://orcid.org/0000-0002-8640-1483
Gurdyal S BesraInstitute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK. g.besra@bham.ac.uk.ORCID http://orcid.org/0000-0002-5605-0395
Zihe RaoShanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0000-0001-9866-2384
Lu ZhangShanghai Institute for Advanced Immunochemical Studies, School of Life Science and Technology, ShanghaiTech University, Shanghai, China. zhanglu1@shanghaitech.edu.cn.ORCID http://orcid.org/0000-0002-4626-5990

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32394010/32394013National Natural Science Foundation of China (National Science Foundation of China) 32394011RCUK | Medical Research Council (MRC) MR/S000542/1, MR/R001154/1
6 · The paper itself

Abstract

Pretomanid and delamanid are prodrugs, whose active derivatives have been reported to target decaprenylphosphoribose-2'-reductase, DprE2, while quabodepistat is a noncovalent inhibitor of decaprenylphosphoribose-2'-oxidase, DprE1. Both enzymes are involved in Mycobacterium tuberculosis cell wall synthesis, but the mechanism of the DprE1-DprE2 epimerase complex and its inhibition by these compounds remain unclear. We report cryo-EM structures of the M. tuberculosis DprE1-DprE2 complex bound with either substrate or quabodepistat in DprE1, and with either activated pretomanid or delamanid in DprE2, respectively. DprE1-DprE2 assembles as a membrane-associated tetramer of a DprE2 dimer flanked on each side by a DprE1 subunit. Both pretomanid and delamanid bind to DprE2 in an NADH-adduct form and within a conserved binding pocket that extends from the NADH-binding site to the substrate-binding site. Quabodepistat binds to DprE1 with a unique mode. Our data reveal the mode of action of these drugs, allowing rational design of new derivatives for improved tuberculosis treatments.

Identifiers

PMID42687039

What OpenQuestion holds

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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.