Evidence map›Paper›PMID 19710017›Full record

ArticleThe Journal of biological chemistry2009

Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis.

Rey-Ting Guo, Yeeting E Chong, Min Guo, Xiang-Lei Yang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. 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
1.2field-weighted citation impact, top 22% 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, 42 citations in OpenAlex.

  1. Article
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  5. Article
  6. Article
  7. Review
  8. Re-evaluation of Diadenosine Tetraphosphate (ApFrontiers in molecular biosciences · 2020
    Review
  9. Peripheral neuropathy via mutant tRNA synthetases: Inhibition of protein translation provides a possible explanation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2016
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
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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

4 authors at 1 institution in 1 country.

Rey-Ting GuoDepartment of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Yeeting E Chong
Min Guo
Xiang-Lei Yang
Scripps Research Institute · US

Funding

INVESTIGATIONS OF REACTIONS OF PHYSIOLOGICAL IMPORTANCER01GM015539 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI SCHIMMEL, PAUL R · 1985 to 2011
$6.6M
Components of Translation in Signal TransductionR01CA092577 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI SCHIMMEL, PAUL R · 2001 to 2016
$4.5M
REACTIONS OF PHYSIOLOGICAL IMPORTANCER37GM015539 · NIGMS · SCRIPPS RESEARCH INSTITUTE · PI SCHIMMEL, PAUL R · 1989 to 1998
–
NCI NIH HHS CA092577NCI NIH HHS R01 CA092577NCRR NIH HHS U54RR025204NIGMS NIH HHS GM015539NIGMS NIH HHS R01 GM015539
6 · The paper itself

Abstract

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs for protein synthesis. However, the aminoacylation reaction can be diverted to produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways. The only known mechanism for Ap4A production by a tRNA synthetase is through the aminoacylation reaction intermediate aminoacyl-AMP, thus making Ap4A synthesis amino acid-dependent. Here, we demonstrate a new mechanism for Ap4A synthesis. Crystal structures and biochemical analyses show that human glycyl-tRNA synthetase (GlyRS) produces Ap4A by direct condensation of two ATPs, independent of glycine concentration. Interestingly, whereas the first ATP-binding pocket is conserved for all class II tRNA synthetases, the second ATP pocket is formed by an insertion domain that is unique to GlyRS, suggesting that GlyRS is the only tRNA synthetase catalyzing direct Ap4A synthesis. A special role for GlyRS in Ap4A homeostasis is proposed.

Indexed as

Adenosine TriphosphateBinding SitesCatalysisChromatography, Thin LayerCrystallography, X-RayDinucleoside PhosphatesGlycineGlycine-tRNA LigaseHomeostasisHumansModels, BiologicalModels, MolecularMolecular ConformationProtein BindingAdenosine Triphosphatediadenosine tetraphosphateDinucleoside PhosphatesGlycineGlycine-tRNA Ligase

Identifiers

PMID19710017
PMCPMC2781443
OpenAlexW2075339499

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.