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Alanine Scan of α-Conotoxin RegIIA Reveals a Selective α3β4 Nicotinic Acetylcholine Receptor Antagonist

Overview of attention for article published in Journal of Biological Chemistry, November 2014
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

news
4 news outlets
blogs
2 blogs
twitter
3 tweeters
googleplus
1 Google+ user
reddit
1 Redditor

Citations

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18 Dimensions

Readers on

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21 Mendeley
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Title
Alanine Scan of α-Conotoxin RegIIA Reveals a Selective α3β4 Nicotinic Acetylcholine Receptor Antagonist
Published in
Journal of Biological Chemistry, November 2014
DOI 10.1074/jbc.m114.605592
Pubmed ID
Authors

Shiva N. Kompella, Andrew Hung, Richard J. Clark, Frank Marí, David J. Adams

Abstract

Activation of the α3β4 nicotinic acetylcholine receptor (nAChR) subtype has recently been implicated in the pathophysiology of various conditions, including development and progression of lung cancer and in nicotine addiction. As selective α3β4 nAChR antagonists, α-conotoxins are valuable tools to evaluate the functional roles of this receptor subtype. We previously reported the discovery of a new α4/7-conotoxin, RegIIA. RegIIA was isolated from Conus regius and inhibits acetylcholine (ACh)-evoked currents mediated by α3β4, α3β2 and α7 nAChR subtypes. The current study used alanine scanning mutation to understand RegIIA's selectivity profile at the α3β4 nAChR subtype. [N11A] and [N12A] RegIIA analogues exhibited three-fold more selectivity for the α3β4 than the α3β2 nAChR subtype. We also report synthesis of [N11A,N12A]RegIIA, a selective α3β4 nAChR antagonist (IC50 of 370 nM) that could potentially be used in the treatment of lung cancer and nicotine addiction. Molecular dynamics simulations of RegIIA and [N11A,N12A]RegIIA bound to α3β4 and α3β2 suggest that destabilization of toxin contacts with a number of residues at both the principal and complementary faces of α3β2 (α3 - Y92, S149, Y189, C192 and Y196; β2 - W57, R81 and F119) may form the molecular basis for the selectivity shift.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 19%
Researcher 3 14%
Unspecified 3 14%
Other 3 14%
Professor 2 10%
Other 6 29%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 24%
Environmental Science 4 19%
Unspecified 4 19%
Medicine and Dentistry 2 10%
Biochemistry, Genetics and Molecular Biology 2 10%
Other 4 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 40. 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 16 January 2015.
All research outputs
#358,884
of 12,366,242 outputs
Outputs from Journal of Biological Chemistry
#293
of 53,824 outputs
Outputs of similar age
#9,520
of 267,084 outputs
Outputs of similar age from Journal of Biological Chemistry
#13
of 620 outputs
Altmetric has tracked 12,366,242 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 53,824 research outputs from this source. They receive a mean Attention Score of 4.2. This one has done particularly well, scoring higher than 99% of its peers.
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 267,084 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 620 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.