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A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases

Overview of attention for article published in Scientific Reports, March 2014
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Title
A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases
Published in
Scientific Reports, March 2014
DOI 10.1038/srep04509
Pubmed ID
Authors

M. Harunur Rashid, Redwan Huq, Mark R. Tanner, Sandeep Chhabra, Keith K. Khoo, Rosendo Estrada, Vikas Dhawan, Satendra Chauhan, Michael W. Pennington, Christine Beeton, Serdar Kuyucak, Raymond S. Norton

Abstract

HsTX1 toxin, from the scorpion Heterometrus spinnifer, is a 34-residue, C-terminally amidated peptide cross-linked by four disulfide bridges. Here we describe new HsTX1 analogues with an Ala, Phe, Val or Abu substitution at position 14. Complexes of HsTX1 with the voltage-gated potassium channels Kv1.3 and Kv1.1 were created using docking and molecular dynamics simulations, then umbrella sampling simulations were performed to construct the potential of mean force (PMF) of the ligand and calculate the corresponding binding free energy for the most stable configuration. The PMF method predicted that the R14A mutation in HsTX1 would yield a > 2 kcal/mol gain for the Kv1.3/Kv1.1 selectivity free energy relative to the wild-type peptide. Functional assays confirmed the predicted selectivity gain for HsTX1[R14A] and HsTX1[R14Abu], with an affinity for Kv1.3 in the low picomolar range and a selectivity of more than 2,000-fold for Kv1.3 over Kv1.1. This remarkable potency and selectivity for Kv1.3, which is significantly up-regulated in activated effector memory cells in humans, suggest that these analogues represent valuable leads in the development of therapeutics for autoimmune diseases.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Mexico 1 2%
Spain 1 2%
Unknown 48 96%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 26%
Student > Ph. D. Student 13 26%
Student > Master 7 14%
Student > Bachelor 6 12%
Professor 3 6%
Other 7 14%
Unknown 1 2%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 38%
Agricultural and Biological Sciences 11 22%
Chemistry 4 8%
Medicine and Dentistry 4 8%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Other 3 6%
Unknown 6 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 October 2015.
All research outputs
#9,986,647
of 12,476,446 outputs
Outputs from Scientific Reports
#40,736
of 57,109 outputs
Outputs of similar age
#129,437
of 191,228 outputs
Outputs of similar age from Scientific Reports
#97
of 159 outputs
Altmetric has tracked 12,476,446 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 57,109 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.3. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 191,228 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 159 others from the same source and published within six weeks on either side of this one. This one is in the 9th percentile – i.e., 9% of its contemporaries scored the same or lower than it.