Evidence map›Paper›PMID 28594916›Full record

ArticlePloS one2017

Identification of key amino acid residues in the hTGR5-nomilin interaction and construction of its binding model.

Takashi Sasaki, Moeko Mita, Naho Ikari, Ayane Kuboyama, Shuzo Hashimoto, Tatsuya Kaneko, Masaji Ishiguro, Makoto Shimizu, Jun Inoue, Ryuichiro Sato

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

5 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. A Gedunin-Type Limonoid, 7-Deacetoxy-7-Oxogedunin, from Andiroba (International journal of molecular sciences · 2022
    Article
  5. 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

10 authors at 3 institutions in 1 country.

Takashi SasakiFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Moeko MitaFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Naho IkariFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Ayane KuboyamaFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Shuzo HashimotoFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Tatsuya KanekoFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Masaji IshiguroDepartment of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashijima, Akiha-ku, Niigata, Japan.
Makoto ShimizuFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Jun InoueFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Ryuichiro SatoFood Biochemistry Laboratory, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-6995-4732
The University of Tokyo · JPJapan Agency for Medical Research and Development · JPNiigata University of Pharmacy and Medical and Life Sciences · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TGR5, a member of the G protein-coupled receptor (GPCR) family, is activated by bile acids. Because TGR5 promotes energy expenditure and improves glucose homeostasis, it is recognized as a key target in treating metabolic diseases. We previously showed that nomilin, a citrus limonoid, activates TGR5 and confers anti-obesity and anti-hyperglycemic effects in mice. Information on the TGR5-nomilin interaction regarding molecular structure, however, has not been reported. In the present study, we found that human TGR5 (hTGR5) shows higher nomilin responsiveness than does mouse TGR5 (mTGR5). Using mouse-human chimeric TGR5, we also found that three amino acid residues (Q77ECL1, R80ECL1, and Y893.29) are important in the hTGR5-nomilin interaction. Based on these results, an hTGR5-nomilin binding model was constructed using in silico docking simulation, demonstrating that four hydrophilic hydrogen-bonding interactions occur between nomilin and hTGR5. The binding mode of hTGR5-nomilin is vastly different from those of other TGR5 agonists previously reported, suggesting that TGR5 forms various binding patterns depending on the type of agonist. Our study promotes a better understanding of the structure of TGR5, and it may be useful in developing and screening new TGR5 agonists.

Indexed as

Models, MolecularAmino AcidsAmino Acid SequenceAnimalsBenzoxepinsHEK293 CellsHumansLimoninsMiceMolecular Docking SimulationMutationReceptors, G-Protein-CoupledSubstrate SpecificityTaurolithocholic AcidAmino AcidsBenzoxepinsGPBAR1 protein, humanLimoninsnomilinobacunoneReceptors, G-Protein-CoupledTaurolithocholic Acid

Identifiers

PMID28594916
PMCPMC5464637
OpenAlexW2624562094

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.