ArticleProceedings of the National Academy of Sciences of the United States of America2014
Molecular determinants of Hv1 proton channel inhibition by guanidine derivatives.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- Functional evidence of Hv1-mediated proton flux in cardiac mitochondria.Channels (Austin, Tex.) · 2026Article
- Spatially Resolved Mapping of Voltage-Gated Proton Channel Activity Reveals Delayed Proton Transport in Local Microenvironments.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modulators of the Human Voltage-Gated Proton Channel HPharmaceuticals (Basel, Switzerland) · 2025Review
- Hv1 channel in immune cells and pharmacology.Pharmacological research · 2025Review
- Validation of HvFrontiers in cellular neuroscience · 2025Article
- Honokiol alleviates monosodium urate-induced gouty pain by inhibiting voltage-gated proton channels in mice.Inflammopharmacology · 2024Article
- Identification of a Novel Structural Class of HJournal of chemical information and modeling · 2024Article
- The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.Aging and disease · 2024Review
- Role of S100 and YKL40 on Intraventricular Cerebral Hemorrhages in the Preterm Infant and the Neuroprotective Role of miR-138- siRNAs-HIF-1a and miR-21-siRNAs-HVCN1 in Neonatal Mice with Nerve Injury.Current medicinal chemistry · 2024Article
- Inhibition of the HFrontiers in immunology · 2024Article
- Trapping Charge Mechanism in Hv1 Channels (International journal of molecular sciences · 2023Article
- Mechanically-primed voltage-gated proton channels from angiosperm plants.Nature communications · 2023Article
- Fifty years of gating currents and channel gating.The Journal of general physiology · 2023Review
- Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems.Neuroscience bulletin · 2023Review
- 5-Chloro-2-Guanidinobenzimidazole (ClGBI) Is a Non-Selective Inhibitor of the Human HPharmaceuticals (Basel, Switzerland) · 2023Article
- Microglial reprogramming by Hv1 antagonism protects neurons from inflammatory and glutamate toxicity.Journal of neurochemistry · 2023Article
- The Voltage-Gated Hv1 HInternational journal of molecular sciences · 2023Article
- Role of voltage-gated proton channel (Hv1) in cancer biology.Frontiers in pharmacology · 2023Review
- The role of Phe150 in human voltage-gated proton channel.iScience · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The voltage-gated proton channel Hv1 plays important roles in proton extrusion, pH homeostasis, and production of reactive oxygen species in a variety of cell types. Excessive Hv1 activity increases proliferation and invasiveness in cancer cells and worsens brain damage in ischemic stroke. The channel is composed of two subunits, each containing a proton-permeable voltage-sensing domain (VSD) and lacking the pore domain typical of other voltage-gated ion channels. We have previously shown that the compound 2-guanidinobenzimidazole (2GBI) inhibits Hv1 proton conduction by binding to the VSD from its intracellular side. Here, we examine the binding affinities of a series of 2GBI derivatives on human Hv1 channels mutated at positions located in the core of the VSD and apply mutant cycle analysis to determine how the inhibitor interacts with the channel. We identify four Hv1 residues involved in the binding: aspartate 112, phenylalanine 150, serine 181, and arginine 211. 2GBI appears to be oriented in the binding site with its benzo ring pointing to F150, its imidazole ring inserted between residue D112 and residues S181 and R211, and the guanidine group positioned in the proximity of R211. We also identify a modified version of 2GBI that is able to reach the binding site on Hv1 from the extracellular side of the membrane. Understanding how compounds like 2GBI interact with the Hv1 channel is an important step to the development of pharmacological treatments for diseases caused by Hv1 hyperactivity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.