Evidence map›Paper›PMID 28846367›Full record

ArticleACS chemical biology2017

Structure and Functional Analysis of ClbQ, an Unusual Intermediate-Releasing Thioesterase from the Colibactin Biosynthetic Pathway.

Naga Sandhya Guntaka, Alan R Healy, Jason M Crawford, Seth B Herzon, Steven D Bruner

Abstract read
In one paragraph

Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

19 citing papers in PubMed.

  1. Article
  2. Article
  3. Current understandings of colibactin regulation.Microbiology (Reading, England) · 2024
    Review
  4. Targeted depletion ofmSystems · 2023
    Article
  5. Article
  6. Review
  7. Thioesterase enzyme families: Functions, structures, and mechanisms.Protein science : a publication of the Protein Society · 2022
    Article
  8. Article
  9. Biosynthesis of depsipeptides, or Depsi: The peptides with varied generations.Protein science : a publication of the Protein Society · 2020
    Review
  10. Structure and bioactivity of colibactin.Bioorganic & medicinal chemistry letters · 2020
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. 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

5 authors.

Naga Sandhya GuntakaDepartment of Chemistry, University of Florida , Gainesville, Florida 32611, United States.
Alan R HealyDepartment of Chemistry, Yale University , New Haven, Connecticut 06520, United States.ORCID 0000-0002-1231-8353
Jason M CrawfordDepartment of Chemistry, Yale University , New Haven, Connecticut 06520, United States.ORCID 0000-0002-7583-1242
Seth B HerzonDepartment of Chemistry, Yale University , New Haven, Connecticut 06520, United States.ORCID 0000-0001-5940-9853
Steven D BrunerDepartment of Chemistry, University of Florida , Gainesville, Florida 32611, United States.ORCID 0000-0002-0522-480X

Funding

Cryptic gut bacterial metabolites that regulate colorectal cancer formationDP2CA186575 · NCI · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2013 to 2013
$2.5M
Synthesis and Study of Complex Antiproliferative and Antimalarial Natural ProductsR01GM110506 · NIGMS · YALE UNIVERSITY · PI HERZON, SETH B. · 2015 to 2018
$1.2M
NCI NIH HHS DP2 CA186575NIGMS NIH HHS R01 GM110506
6 · The paper itself

Abstract

Colibactin is a genotoxic hybrid nonribosomal peptide/polyketide secondary metabolite produced by various pathogenic and probiotic bacteria residing in the human gut. The presence of colibactin metabolites has been correlated to colorectal cancer formation in several studies. The specific function of many gene products in the colibactin gene cluster can be predicted. However, the role of ClbQ, a type II editing thioesterase, has not been established. The importance of ClbQ has been demonstrated by genetic deletions that abolish colibactin cytotoxic activity, and recent studies suggest an atypical role in releasing pathway intermediates from the assembly line. Here we report the 2.0 Å crystal structure and biochemical characterization of ClbQ. Our data reveal that ClbQ exhibits greater catalytic efficiency toward acyl-thioester substrates as compared to precolibactin intermediates and does not discriminate among carrier proteins. Cyclized pyridone-containing colibactins, which are off-pathway derivatives, are not viable substrates for ClbQ, while linear precursors are, supporting a role of ClbQ in facilitating the promiscuous off-loading of premature precolibactin metabolites and novel insights into colibactin biosynthesis.

Indexed as

Bacterial ProteinsCrystallography, X-RayGene Expression Regulation, BacterialGene Expression Regulation, EnzymologicModels, MolecularPeptidesPolyketidesProtein ConformationThiolester HydrolasesBacterial ProteinscolibactinPeptidesPolyketidesThiolester Hydrolases

Identifiers

PMID28846367
PMCPMC5830302

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.