Evidence map›Paper›PMID 29606590›Full record

ArticleMolecular cell2018

Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3).

Wei Lin, Kalyan Das, David Degen, Abhishek Mazumder, Diego Duchi, Dongye Wang, Yon W Ebright, Richard Y Ebright, Elena Sineva, Matthew Gigliotti and 13 more

Abstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 3% of its field
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

64 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.

  1. Fidaxomicin resistance inAntimicrobial agents and chemotherapy · 2024
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Future Research Directions on Mycobacterium tuberculosis Proteins.Advances in experimental medicine and biology · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Switching Residues: A Platform for the Synthesis of Fidaxomicin Antibiotics.Angewandte Chemie (International ed. in English) · 2025
    Article
  12. Article
  13. APlants (Basel, Switzerland) · 2025
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

4 more citing papers are in PubMed but not listed here.

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

23 authors at 5 institutions in 4 countries.

Wei LinWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Kalyan DasRega Institute and Department of Microbiology and Immunology, KU Leuven, 3000 Leuven, Belgium. Electronic address: kalyan.das@kuleuven.be.
David DegenWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Abhishek MazumderWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Diego DuchiDepartment of Physics, University of Oxford, Oxford OX1 3PU, UK.
Dongye WangWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Yon W EbrightWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Richard Y EbrightWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Elena SinevaWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Matthew GigliottiWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Aashish SrivastavaWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Sukhendu MandalWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Yi JiangWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Yu LiuWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Ruiheng YinWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA.
Zhening ZhangThe National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York NY 10027, USA.
Edward T EngThe National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York NY 10027, USA.
Dennis ThomasCenter for Integrative Proteomics, Rutgers University, Piscataway, NJ 08854, USA.
Stefano DonadioNAICONS Srl., 20139 Milan, Italy.
Haibo ZhangSouth China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
Changsheng ZhangSouth China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
Achillefs N KapanidisDepartment of Physics, University of Oxford, Oxford OX1 3PU, UK.
Richard H EbrightWaksman Institute and Department of Chemistry, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: ebright@waksman.rutgers.edu.
Rutgers, The State University of New Jersey · USChinese Academy of Sciences · CNNew York Structural Biology Center · USUniversity of Oxford · GBRega Institute for Medical Research · BE

Funding

Therapeutics for drug resistant-bacteria: Arylpropionyl-phloroglucinolsU19AI109713 · NIAID · RBHS-NEW JERSEY MEDICAL SCHOOL · PI ALLAND, DAVID · 2014 to 2018
$26.9M
TRD #3: An automated and streamlined pipeline for in-situ molecular microscopyP41GM103310 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI DE MARCO, ALEX, KIEFT, JEFFREY S · 2012 to 2021
$14.7M
TRANSCRIPTION ACTIVATION BY CAPR01GM041376 · NIGMS · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI RICHARD H. EBRIGHT · 1989 to 2026
$6.5M
Therapeutics for Drug-Resistant Bacteria: PseudouridimycinsR01AI104660 · NIAID · RUTGERS, THE STATE UNIV OF N.J. · PI EBRIGHT, RICHARD H. · 2013 to 2017
$5.1M
BACTERIAL TRANSCRIPTION COMPLEXESR37GM041376 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI EBRIGHT, RICHARD H. · 2013 to 2022
$5.0M
Biotechnology and Biological Sciences Research Council BB/H01795X/1NIAID NIH HHS R01 AI104660NIAID NIH HHS U19 AI109713NIGMS NIH HHS P41 GM103310NIGMS NIH HHS R01 GM041376NIGMS NIH HHS R37 GM041376
6 · The paper itself

Abstract

Fidaxomicin is an antibacterial drug in clinical use for treatment of Clostridium difficile diarrhea. The active ingredient of fidaxomicin, lipiarmycin A3 (Lpm), functions by inhibiting bacterial RNA polymerase (RNAP). Here we report a cryo-EM structure of Mycobacterium tuberculosis RNAP holoenzyme in complex with Lpm at 3.5-Å resolution. The structure shows that Lpm binds at the base of the RNAP "clamp." The structure exhibits an open conformation of the RNAP clamp, suggesting that Lpm traps an open-clamp state. Single-molecule fluorescence resonance energy transfer experiments confirm that Lpm traps an open-clamp state and define effects of Lpm on clamp dynamics. We suggest that Lpm inhibits transcription by trapping an open-clamp state, preventing simultaneous interaction with promoter -10 and -35 elements. The results account for the absence of cross-resistance between Lpm and other RNAP inhibitors, account for structure-activity relationships of Lpm derivatives, and enable structure-based design of improved Lpm derivatives.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsBinding SitesCryoelectron MicroscopyDNA-Directed RNA PolymerasesDrug DesignDrug Resistance, BacterialEscherichia coliFidaxomicinFluorescence Resonance Energy TransferGene Expression Regulation, BacterialModels, MolecularMutationMycobacterium tuberculosisProtein BindingProtein ConformationAnti-Bacterial AgentsBacterial ProteinsDNA-Directed RNA PolymerasesFidaxomicinantibioticcryo-electron microscopyfidaxomicinlipiarmycinMycobacterium tuberculosisRNA polymeraseRNA polymerase clampRNA polymerase inhibitorRNA polymerase switch regionsingle-molecule fluorescence resonance energy transfer

Identifiers

PMID29606590
PMCPMC6205224
OpenAlexW2781904465

What OpenQuestion holds

Textmetadata
LicenceTDM
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.