ArticleThe Journal of membrane biology2011
Mechanistic insight into the h(2)o/d (2)o isotope effect in the proton transport of the influenza virus m2 protein.
Article in The Journal of membrane biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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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.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Proton Transport Mechanism of M2 Proton Channel Studied by Laser-Induced pH Jump.Journal of the American Chemical Society · 2017Article
- Theoretical frameworks for multiscale modeling and simulation.Current opinion in structural biology · 2014Review
- Philosophy of voltage-gated proton channels.Journal of the Royal Society, Interface · 2014Review
- Article
- Article
- Modeling the membrane environment has implications for membrane protein structure and function: influenza A M2 protein.Protein science : a publication of the Protein Society · 2013Review
- M2 protein from influenza A: from multiple structures to biophysical and functional insights.Current opinion in virology · 2012Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
The M2 proton channel is essential for the replication of the flu virus and is a known drug target. The functional mechanism of channel activation and conductance is key to both the basic biology of viral replication and the design of drugs that can withstand mutations. A quantitative model was previously developed for calculating the rate of proton transport through the M2 channel. The permeant proton was assumed to diffuse to the pore, obligatorily bind to the His37 tetrad, and then dissociate and be released to either side of the tetrad. Here the model is used to calculate the effect of a change in solvent from H(2)O to D(2)O on the rate of proton transport. The solvent substitution affects two parameters in the model: the proton diffusion constant and the pK (a) for proton binding to the His37 tetrad. When the known effects on these two parameters are included, the deuterium isotope effect calculated from the model is in quantitatively agreement with experimental results. This strict test of the theoretical model provides strong support for the hypothesis that the permeant proton obligatorily binds to and then unbinds from the His37 tetrad. This putatively essential role of the His37 tetrad in the functional mechanism of the M2 channel makes it a promising target for designing mutation-tolerant drugs.
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Registered trials
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