Evidence map›Paper›PMID 29867143›Full record

ArticleNature chemical biology2018

Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme.

Nan Wang, Jeffrey D Rudolf, Liao-Bin Dong, Jerzy Osipiuk, Catherine Hatzos-Skintges, Michael Endres, Chin-Yuan Chang, Gyorgy Babnigg, Andrzej Joachimiak, George N Phillips and 1 more

Open access · greenAbstract read
In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Bacterial terpenome.Natural product reports · 2021
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Structural genomics and the Protein Data Bank.The Journal of biological chemistry
    Review
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

11 authors at 3 institutions in 1 country.

Nan WangDepartment of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.
Jeffrey D RudolfDepartment of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.ORCID http://orcid.org/0000-0003-2718-9651
Liao-Bin DongDepartment of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.ORCID http://orcid.org/0000-0002-2943-1299
Jerzy OsipiukMidwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL, USA.
Catherine Hatzos-SkintgesMidwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL, USA.
Michael EndresMidwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL, USA.
Chin-Yuan ChangDepartment of Chemistry, The Scripps Research Institute, Jupiter, FL, USA.
Gyorgy BabniggMidwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL, USA.
Andrzej JoachimiakMidwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL, USA.
George N PhillipsDepartment of Biosciences, Rice University, Houston, TX, USA.
Ben ShenDepartment of Chemistry, The Scripps Research Institute, Jupiter, FL, USA. shenb@scripps.edu.ORCID http://orcid.org/0000-0002-9750-5982
Argonne National Laboratory · USScripps Research Institute · USRice University · US

Funding

Midwest Center for Structural GenomicsU54GM094585 · NIGMS · UNIVERSITY OF CHICAGO · PI MINOR, WLADEK · 2010 to 2014
$33.7M
Enzyme Discovery for Natural Product BiosynthesisU01GM098248 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI PHILLIPS, GEORGE NEAL · 2011 to 2015
$2.8M
Discovery and biosynthesis of diterpenoid natural products in actinomycetalsR01GM114353 · NIGMS · SCRIPPS FLORIDA · PI SHEN, BEN · 2016 to 2019
$1.8M
Rigidity and flexibility of large bio-molecular assembliesR01GM109456 · NIGMS · SMITH COLLEGE · PI STREINU, ILEANA · 2013 to 2017
$1.4M
NIGMS NIH HHS R01 GM109456NIGMS NIH HHS R01 GM114353NIGMS NIH HHS U01 GM098248NIGMS NIH HHS U54 GM094585
6 · The paper itself

Abstract

Acyl-coenzyme A (CoA) ligases catalyze the activation of carboxylic acids via a two-step reaction of adenylation followed by thioesterification. Here, we report the discovery of a non-adenylating acyl-CoA ligase PtmA2 and the functional separation of an acyl-CoA ligase reaction. Both PtmA1 and PtmA2, two acyl-CoA ligases from the biosynthetic pathway of platensimycin and platencin, are necessary for the two steps of CoA activation. Gene inactivation of ptmA1 and ptmA2 resulted in the accumulation of free acid and adenylate intermediates, respectively. Enzymatic and structural characterization of PtmA2 confirmed its ability to only catalyze thioesterification. Structural characterization of PtmA2 revealed it binds both free acid and adenylate substrates and undergoes the established mechanism of domain alternation. Finally, site-directed mutagenesis restored both the adenylation and complete CoA activation reactions. This study challenges the currently accepted paradigm of adenylating enzymes and inspires future investigations on functionally separated acyl-CoA ligases and their ramifications in biology.

Indexed as

BiocatalysisCarboxylic AcidsCoenzyme A LigasesEstersModels, MolecularMolecular StructureSulfhydryl CompoundsCarboxylic AcidsCoenzyme A LigasesEstersSulfhydryl Compounds

Identifiers

PMID29867143
PMCPMC6008203
OpenAlexW2806460700

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.