Evidence map›Paper›PMID 26396194›Full record

ArticleThe Journal of biological chemistry2015

Structural Basis for the Regulation of the MmpL Transporters of Mycobacterium tuberculosis.

Jared A Delmar, Tsung-Han Chou, Catherine C Wright, Meredith H Licon, Julia K Doh, Abhijith Radhakrishnan, Nitin Kumar, Hsiang-Ting Lei, Jani Reddy Bolla, Kanagalaghatta R Rajashankar and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

18 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023
    Review
  5. M. tuberculosis AlkX Encoded byMicrobiology spectrum · 2022
    Article
  6. Article
  7. Transcriptional regulation and drug resistance inFrontiers in cellular and infection microbiology · 2022
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Insights onFrontiers in microbiology · 2018
    Article
  15. Article
  16. Article
  17. Crystal structure of the Mycobacterium tuberculosis transcriptional regulator Rv0302.Protein science : a publication of the Protein Society · 2015
    Article
  18. 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

13 authors at 3 institutions in 1 country.

Jared A DelmarDepartments of Physics and Astronomy, Iowa State University, Ames, Iowa 50011.
Tsung-Han ChouDepartments of Physics and Astronomy, Iowa State University, Ames, Iowa 50011.
Catherine C WrightDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon 97239.
Meredith H LiconDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon 97239.
Julia K DohDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon 97239.
Abhijith RadhakrishnanDepartments of Chemistry, Iowa State University, Ames, Iowa 50011.
Nitin KumarDepartments of Chemistry, Iowa State University, Ames, Iowa 50011.
Hsiang-Ting LeiDepartments of Chemistry, Iowa State University, Ames, Iowa 50011.
Jani Reddy BollaDepartments of Chemistry, Iowa State University, Ames, Iowa 50011.
Kanagalaghatta R RajashankarNortheastern Collaborative Access Team and Department of Chemistry and Chemical Biology, Cornell University, Argonne National Laboratory, Argonne, Illinois 60439.
Chih-Chia SuDepartments of Physics and Astronomy, Iowa State University, Ames, Iowa 50011.
Georgiana E PurdyDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon 97239.
Edward W YuDepartments of Physics and Astronomy, Iowa State University, Ames, Iowa 50011; Departments of Chemistry, Iowa State University, Ames, Iowa 50011. Electronic address: ewyu@iastate.edu.
Iowa State University · USOregon Health & Science University · USArgonne National Laboratory · US

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Pixel Array Detector for X-ray CrystallographyS10RR029205 · NCRR · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2010 to 2010
$1.8M
Mtb regulators of essential and virulence-associated MmpLsR56AI114664 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI PURDY, GEORGIANA E., YU, EDWARD W · 2015 to 2015
$476k
NCRR NIH HHS S10 RR029205NIAID NIH HHS R56 AI114664NIAID NIH HHS R56AI114664NIGMS NIH HHS P41 GM103403
6 · The paper itself

Abstract

The mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the MmpL (mycobacterial membrane protein large) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complex regulatory network, including the TetR family transcriptional regulators Rv3249c and Rv1816. Here we report the crystal structures of these two regulators, revealing dimeric, two-domain molecules with architecture consistent with the TetR family of regulators. Buried extensively within the C-terminal regulatory domains of Rv3249c and Rv1816, we found fortuitous bound ligands, which were identified as palmitic acid (a fatty acid) and isopropyl laurate (a fatty acid ester), respectively. Our results suggest that fatty acids may be the natural ligands of these regulatory proteins. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by these proteins. Binding of palmitic acid renders these regulators incapable of interacting with their respective operator DNAs, which will result in derepression of the corresponding mmpL genes. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters.

Indexed as

Bacterial ProteinsCrystallography, X-RayMembrane Transport ProteinsMycobacterium tuberculosisProtein ConformationBacterial ProteinsMembrane Transport Proteinsbacterial pathogenesiscell wallmycobacterial membrane protein largemycobacterial membrane protein smallMycobacterium tuberculosisRv3249cTetR family regulatorstranscription repressorx-ray crystallography

Identifiers

PMID26396194
PMCPMC4653710
OpenAlexW2174860010

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.