A mutational and molecular dynamics study of the cys-loop GABA receptor Hco-UNC-49 from Haemonchus contortus: Agonist recognition in the nematode GABA receptor family.

Josh Foster, Everett Cochrane, Mohammad Hassan Khatami, Sarah A Habibi, Hendrick de Haan, Sean G Forrester

Open access · goldAbstract read

In one paragraph

Article in International journal for parasitology. Drugs and drug resistance, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

0.5field-weighted citation impact, top 30% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

Anthelmintics - From Discovery to Resistance III (Indian Rocks Beach, FL, 2018).International journal for parasitology. Drugs and drug resistance · 2018
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

6 authors at 1 institution in 1 country.

Josh FosterFaculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4, Canada.

Everett CochraneFaculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4, Canada.

Mohammad Hassan KhatamiFaculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4, Canada.

Sarah A HabibiFaculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4, Canada.

Hendrick de HaanFaculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4, Canada.

Sean G ForresterFaculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North, Oshawa, ON, L1H 7K4, Canada. Electronic address: sean.forrester@uoit.ca.

Ontario Tech University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The UNC-49 receptor is a unique nematode γ-aminobutyric acid (GABA)-gated chloride channel that may prove to be a novel target for the development of nematocides. Here we have characterized various charged amino acid residues in and near the agonist binding site of the UNC-49 receptor from the parasitic nematode Haemonchus contorts. Utilizing the Caenorhabditis elegans GluCl crystal structure as a template, a model was generated and various charged residues [D83 (loop D), E131 (loop A), H137 (pre-loop E), R159 (Loop E), E185 (Loop B) and R241 (Loop C)] were investigated based on their location and conservation. These residues may contribute to structure, function, and molecular interactions with agonists. It was found that all residues chosen were important for receptor function to varying degrees. Results of the mutational analysis and molecular simulations suggest that R159 may be interacting with D83 by an ionic interaction that may be crucial for general GABA receptor function. We have used the results from this study as well as knowledge of residues involved in GABA receptor binding to identify sequence patterns that may assist in understanding the function of lesser known GABA receptor subunits from parasitic nematodes.

Indexed as

MutationAnimalsAntinematodal AgentsBinding SitesCaenorhabditis elegansCaenorhabditis elegans ProteinsCrystallizationGABA-A Receptor AgonistsHaemonchusHelminth ProteinsIon Channel GatingMolecular Dynamics SimulationProtein BindingReceptors, GABAReceptors, GABA-AXenopus laevisAntinematodal AgentsCaenorhabditis elegans ProteinsGABA-A Receptor AgonistsHelminth ProteinsReceptors, GABAReceptors, GABA-AUnc-49 protein, C elegansAgonist recognitionHaemonchus contortusMolecular dynamicsMutagenesisUNC-49 GABA receptor

Identifiers

PMID30361167

DOI10.1016/j.ijpddr.2018.10.001

PMCPMC6287672

OpenAlexW2895194524

What OpenQuestion holds

Textmetadata

LicenceCC BY-NC-ND

Read underepoch 390

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.