Evidence map›Paper›PMID 33196887›Full record

ArticleThe Journal of membrane biology2021

Thermodynamics and Mechanism of the Membrane Permeation of Hv1 Channel Blockers.

Victoria T Lim, J Alfredo Freites, Francesco Tombola, Douglas J Tobias

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

Article in The Journal of membrane biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Quantitative insights into the mechanism of proton conduction and selectivity for the human voltage-gated proton channel Hv1.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  2. Article
  3. Review
  4. Reduced HProceedings of the National Academy of Sciences of the United States of America · 2022
    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

4 authors at 1 institution in 1 country.

Victoria T LimDepartment of Chemistry, University of California, Irvine, USA.
J Alfredo FreitesDepartment of Chemistry, University of California, Irvine, USA.
Francesco TombolaDepartment of Physiology and Biophysics, University of California, Irvine, CA, 92697, USA.
Douglas J TobiasDepartment of Chemistry, University of California, Irvine, USA. dtobias@uci.edu.
University of California, Irvine · US

Funding

Mechanisms of Permeation and Gating of Voltage-Sensing DomainsR01GM098973 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI TOMBOLA, FRANCESCO · 2011 to 2025
$4.5M
NIGMS NIH HHS R01 GM098973
6 · The paper itself

Abstract

The voltage-gated proton channel Hv1 mediates efflux of protons from the cell. Hv1 integrally contributes to various physiological processes including pH homeostasis and the respiratory burst of phagocytes. Inhibition of Hv1 may provide therapeutic avenues for the treatment of inflammatory diseases, breast cancer, and ischemic brain damage. In this work, we investigate two prototypical Hv1 inhibitors, 2-guanidinobenzimidazole (2GBI), and 5-chloro-2-guanidinobenzimidazole (GBIC), from an experimentally screened class of guanidine derivatives. Both compounds block proton conduction by binding the same site located on the intracellular side of the channel. However, when added to the extracellular medium, the compounds strongly differ in their ability to inhibit proton conduction, suggesting substantial differences in membrane permeability. Here, we compute the potential of mean force for each compound to permeate through the membrane using atomistic molecular dynamics simulations with the adaptive biasing force method. Our results rationalize the putative distinction between these two blockers with respect to their abilities to permeate the cellular membrane.

Indexed as

ThermodynamicsCell Membrane PermeabilityIon ChannelsMolecular Dynamics SimulationProtonsIon ChannelsProtons2gbiAdaptive biasing forceHv1Membrane permeabilityMolecular dynamicsPotential of mean force

Identifiers

PMID33196887
PMCPMC8549822
OpenAlexW3099449254

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.