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Ordering a Dynamic Protein Via a Small-Molecule Stabilizer

Overview of attention for article published in Journal of the American Chemical Society, February 2013
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  • Good Attention Score compared to outputs of the same age (66th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Citations

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112 Mendeley
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Title
Ordering a Dynamic Protein Via a Small-Molecule Stabilizer
Published in
Journal of the American Chemical Society, February 2013
DOI 10.1021/ja3122334
Pubmed ID
Authors

Ningkun Wang, Chinmay Y. Majmudar, William C. Pomerantz, Jessica K. Gagnon, Jack D. Sadowsky, Jennifer L. Meagher, Taylor K. Johnson, Jeanne A. Stuckey, Charles L. Brooks, James A. Wells, Anna K. Mapp

Abstract

Like many coactivators, the GACKIX domain of the master coactivator CBP/p300 recognizes transcriptional activators of diverse sequence composition via dynamic binding surfaces. The conformational dynamics of GACKIX that underlie its function also render it especially challenging for structural characterization. We have found that the ligand discovery strategy of Tethering is an effective method for identifying small-molecule fragments that stabilize the GACKIX domain, enabling for the first time the crystallographic characterization of this important motif. The 2.0 Å resolution structure of GACKIX complexed to a small molecule was further analyzed by molecular dynamics simulations, which revealed the importance of specific side-chain motions that remodel the activator binding site in order to accommodate binding partners of distinct sequence and size. More broadly, these results suggest that Tethering can be a powerful strategy for identifying small-molecule stabilizers of conformationally malleable proteins, thus facilitating their structural characterization and accelerating the discovery of small-molecule modulators.

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X Demographics

The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 112 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Italy 1 <1%
France 1 <1%
Canada 1 <1%
Unknown 108 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 40 36%
Researcher 21 19%
Student > Doctoral Student 7 6%
Professor 6 5%
Other 6 5%
Other 21 19%
Unknown 11 10%
Readers by discipline Count As %
Chemistry 53 47%
Agricultural and Biological Sciences 18 16%
Biochemistry, Genetics and Molecular Biology 16 14%
Unspecified 3 3%
Computer Science 2 2%
Other 5 4%
Unknown 15 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 25 March 2013.
All research outputs
#7,787,627
of 24,189,858 outputs
Outputs from Journal of the American Chemical Society
#29,688
of 64,261 outputs
Outputs of similar age
#63,601
of 196,284 outputs
Outputs of similar age from Journal of the American Chemical Society
#293
of 567 outputs
Altmetric has tracked 24,189,858 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 64,261 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has gotten more attention than average, scoring higher than 53% 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 196,284 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.
We're also able to compare this research output to 567 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.