Evidence map›Paper›PMID 24953769›Full record

ArticleBiochimica et biophysica acta2014

Conformational dynamics of human FXR-LBD ligand interactions studied by hydrogen/deuterium exchange mass spectrometry: insights into the antagonism of the hypolipidemic agent Z-guggulsterone.

Liping Yang, David Broderick, Yuan Jiang, Victor Hsu, Claudia S Maier

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. On the Cholesterol Raising Effect of Coffee Diterpenes Cafestol and 16-International journal of molecular sciences · 2024
    Article
  3. Review
  4. Article
  5. Farnesoid X receptor (FXR): Structures and ligands.Computational and structural biotechnology journal · 2021
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. 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.

Liping YangDepartment of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
David BroderickDepartment of Chemistry, Oregon State University, Corvallis, OR 97331, USA.
Yuan JiangDepartment of Statistics, Oregon State University, Corvallis, OR 97331, USA.
Victor HsuBiochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
Claudia S MaierDepartment of Chemistry, Oregon State University, Corvallis, OR 97331, USA. Electronic address: claudia.maier@oregonstate.edu.

Funding

Reducing Susceptibility to Environmental Stress Throughout the Life SpanP30ES000210 · NIEHS · OREGON STATE UNIVERSITY · PI BECKMAN, JOSEPH S · 1985 to 2015
$21.4M
Ion Mobility Time-of-flight Mass Spectrometry SystemS10RR025628 · NCRR · OREGON STATE UNIVERSITY · PI MAIER, CLAUDIA S, STEVENS, JAN FREDERIK · 2009 to 2009
$440k
NCRR NIH HHS S10 RR025628NCRR NIH HHS S10RR025628NIEHS NIH HHS P30 ES000210NIEHS NIH HHS P30ES000210
6 · The paper itself

Abstract

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of transcription factors that plays a key role in the regulation of bile acids, lipid and glucose metabolisms. The regulative function of FXR is governed by conformational changes of the ligand binding domain (LBD) upon ligand binding. Although FXR is a highly researched potential therapeutic target, only a limited number of FXR-agonist complexes have been successfully crystallized and subsequently yielded high resolution structures. There is currently no structural information of any FXR-antagonist complexes publically available. We therefore explored the use of amide hydrogen/deuterium exchange (HDX) coupled with mass spectrometry for characterizing conformational changes in the FXR-LBD upon ligand binding. Ligand-specific deuterium incorporation profiles were obtained for three FXR ligand chemotypes: GW4064, a synthetic non-steroidal high affinity agonist; the bile acid chenodeoxycholic acid (CDCA), the endogenous low affinity agonist of FXR; and Z-guggulsterone (GG), an in vitro antagonist of the steroid chemotype. A comparison of the HDX profiles of their ligand-bound FXR-LBD complexes revealed a unique mode of interaction for GG. The conformational features of the FXR-LBD-antagonist interaction are discussed.

Indexed as

Amino Acid SequenceChenodeoxycholic AcidDeuterium Exchange MeasurementEscherichia coliHumansHypolipidemic AgentsIsoxazolesLigandsMass SpectrometryMolecular Docking SimulationMolecular Sequence DataPregnenedionesProtein Structure, SecondaryProtein Structure, TertiaryReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearChenodeoxycholic AcidGW 4064Hypolipidemic AgentsIsoxazolesLigandspregna-4,17-diene-3,16-dionePregnenedionesReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearRecombinant ProteinsConformational dynamicsFarnesoid X receptorGuggulsteroneHydrogen/deuterium exchangeLigand interactionMass spectrometry

Identifiers

PMID24953769
PMCPMC4137978

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.