Evidence map›Paper›PMID 27244450›Full record

ArticlePloS one2016

Investigating the Role of Loop C Hydrophilic Residue 'T244' in the Binding Site of ρ1 GABAC Receptors via Site Mutation and Partial Agonism.

Moawiah M Naffaa, Nathan Absalom, V Raja Solomon, Mary Chebib, David E Hibbs, Jane R Hanrahan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Pharmacological Effect of GABA Analogues on GABA-Life (Basel, Switzerland) · 2022
    Article
  2. Article
  3. 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

6 authors at 1 institution in 1 country.

Moawiah M NaffaaFaculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Nathan AbsalomFaculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
V Raja SolomonFaculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Mary ChebibFaculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
David E HibbsFaculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Jane R HanrahanFaculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.
University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The loop C hydrophilic residue, threonine 244 lines the orthosteric binding site of ρ1 GABAC receptors was studied by point mutation into serine, alanine and cysteine, and tested with GABA, some representative partial agonists and antagonists. Thr244 has a hydroxyl group essential for GABA activity that is constrained by the threonine methyl group, orienting it toward the binding site. Significant decreases in activation effects of the studied ligands at ρ1 T244S mutant receptors, suggests a critical role for this residue. Results of aliphatic and heteroaromatic partial agonists demonstrate different pharmacological effects at ρ1 T244S mutant receptors when co-applied with GABA EC50 responses. ρ1 T244A and ρ1 T244C mutant receptors have minimal sensitivity to GABA at high mM concentrations, whereas, the ρ1 WT partial agonists, β-alanine and MTSEA demonstrate more efficacy and potency, respectively, than GABA at these mutant receptors. This study explores the role of Thr244 in the binding of agonists as an initial step during channel gating by moving loop C towards the ligand.

Indexed as

Amino Acid SequenceAmino Acids, NeutralAnimalsbeta-AlanineBinding SitesGABA AgonistsGABA AntagonistsGlycineHumansIsonicotinic AcidsLigand-Gated Ion ChannelsMolecular Docking SimulationPatch-Clamp TechniquesPoint MutationProtein ConformationReceptors, GABA5-aminovaleric acidAmino Acids, Neutralbeta-AlanineGABA AgonistsGABA AntagonistsGABA-C receptorGlycineisoguvacineIsonicotinic AcidsLigand-Gated Ion ChannelsReceptors, GABA

Identifiers

PMID27244450
PMCPMC4887073
OpenAlexW2416428099

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.