Evidence map›Paper›PMID 34242558›Full record

ArticleStructure (London, England : 1993)2021

Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target.

Oliver Adams, Justin C Deme, Joanne L Parker, CRyPTIC Consortium, Philip W Fowler, Susan M Lea, Simon Newstead

Abstract read
In one paragraph

Article in Structure (London, England : 1993), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing 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

42 citing papers in PubMed.

  1. Structure, assembly, and mechanism of the MmpL family of transporters.Microbiology and molecular biology reviews : MMBR · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Bacterial cell envelope-targeting antibiotics.Nature reviews. Microbiology · 2026
    Review
  6. Structural elucidation of the hexameric MmpS4-MmpL4 complex frombioRxiv : the preprint server for biology · 2026
    Article
  7. Cryo-EM structures of mycobacteria MmpL5-AcpM complex.Science China. Life sciences · 2025
    Article
  8. Thienopyrimidine amide analogs target MmpL3 inAntimicrobial agents and chemotherapy · 2025
    Article
  9. Article
  10. Structural and functional analysis of theProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Journal of the American Chemical Society · 2025
    Article
  15. Article
  16. bioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Frontiers in microbiology · 2025
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Oliver AdamsDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Justin C DemeThe Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK; Central Oxford Structural Molecular Imaging Centre (COSMIC), University of Oxford, Oxford OX1 3RE, UK; Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA.
Joanne L ParkerDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
CRyPTIC Consortium
Philip W FowlerNuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK; National Institute of Health Research (NIHR) Oxford Biomedical Research Centre, John Radcliffe, Oxford OX3 9DU, UK.
Susan M LeaThe Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK; Central Oxford Structural Molecular Imaging Centre (COSMIC), University of Oxford, Oxford OX1 3RE, UK; Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA. Electronic address: susan.lea@nih.gov.
Simon NewsteadDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; The Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford OX1 3QU, UK. Electronic address: simon.newstead@bioch.ox.ac.uk.

Funding

Biotechnology and Biological Sciences Research Council BB/M011224/1Department of HealthMedical Research Council MR/M011984/1Medical Research Council MR/S021043/1Wellcome Trust 100298Wellcome Trust 200205/Z/15/ZWellcome Trust 201536Wellcome Trust 209194Wellcome Trust 209194/Z/17/ZWellcome Trust 215519Wellcome Trust 219531
6 · The paper itself

Abstract

Tuberculosis (TB) is the leading cause of death from a single infectious agent and in 2019 an estimated 10 million people worldwide contracted the disease. Although treatments for TB exist, continual emergence of drug-resistant variants necessitates urgent development of novel antituberculars. An important new target is the lipid transporter MmpL3, which is required for construction of the unique cell envelope that shields Mycobacterium tuberculosis (Mtb) from the immune system. However, a structural understanding of the mutations in Mtb MmpL3 that confer resistance to the many preclinical leads is lacking, hampering efforts to circumvent resistance mechanisms. Here, we present the cryoelectron microscopy structure of Mtb MmpL3 and use it to comprehensively analyze the mutational landscape of drug resistance. Our data provide a rational explanation for resistance variants local to the central drug binding site, and also highlight a potential alternative route to resistance operating within the periplasmic domain.

Indexed as

Drug Resistance, BacterialBacterial ProteinsCryoelectron MicroscopyMembrane Transport ProteinsMutationBacterial ProteinsMembrane Transport ProteinsMmpL3 protein, Mycobacterium tuberculosisantitubercularcryo-EMdrug resistanceLMNGmembrane proteinMmpLMmpL3mycolic acidRND transportertuberculosis

Identifiers

PMID34242558
PMCPMC8752444

What OpenQuestion holds

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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.