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A new tool for the chemical genetic investigation of the Plasmodium falciparum Pfnek-2 NIMA-related kinase

Overview of attention for article published in Malaria Journal, November 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (69th percentile)
  • Good Attention Score compared to outputs of the same age and source (69th percentile)

Mentioned by

twitter
7 tweeters

Citations

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4 Dimensions

Readers on

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20 Mendeley
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Title
A new tool for the chemical genetic investigation of the Plasmodium falciparum Pfnek-2 NIMA-related kinase
Published in
Malaria Journal, November 2016
DOI 10.1186/s12936-016-1580-3
Pubmed ID
Authors

Deborah F. Mitcheson, Andrew R. Bottrill, Katherine Carr, Christopher R. Coxon, Celine Cano, Bernard T. Golding, Roger J. Griffin, Andrew M. Fry, Christian Doerig, Richard Bayliss, Andrew B. Tobin

Abstract

Examining essential biochemical pathways in Plasmodium falciparum presents serious challenges, as standard molecular techniques such as siRNA cannot be employed in this organism, and generating gene knock-outs of essential proteins requires specialized conditional approaches. In the study of protein kinases, pharmacological inhibition presents a feasible alternative option. However, as in mammalian systems, inhibitors often lack the desired selectivity. Described here is a chemical genetic approach to selectively inhibit Pfnek-2 in P. falciparum, a member of the NIMA-related kinase family that is essential for completion of the sexual development of the parasite. Introduction of a valine to cysteine mutation at position 24 in the glycine rich loop of Pfnek-2 does not affect kinase activity but confers sensitivity to the protein kinase inhibitor 4-(6-ethynyl-9H-purin-2-ylamino) benzene sulfonamide (NCL-00016066). Using a combination of in vitro kinase assays and mass spectrometry, (including phosphoproteomics) the study shows that this compound acts as an irreversible inhibitor to the mutant Pfnek2 likely through a covalent link with the introduced cysteine residue. In particular, this was shown by analysis of total protein mass using mass spectrometry which showed a shift in molecular weight of the mutant kinase in the presence of the inhibitor to be precisely equivalent to the molecular weight of NCL-00016066. A similar molecular weight shift was not observed in the wild type kinase. Importantly, this inhibitor has little activity towards the wild type Pfnek-2 and, therefore, has all the properties of an effective chemical genetic tool that could be employed to determine the cellular targets for Pfnek-2. Allelic replacement of wild-type Pfnek-2 with the mutated kinase will allow for targeted inhibition of Pfnek-2 with NCL-00016066 and hence pave the way for comparative studies aimed at understanding the biological role and transmission-blocking potential of Pfnek-2.

Twitter Demographics

The data shown below were collected from the profiles of 7 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 20 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 30%
Researcher 4 20%
Other 2 10%
Student > Bachelor 1 5%
Lecturer > Senior Lecturer 1 5%
Other 2 10%
Unknown 4 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 20%
Agricultural and Biological Sciences 4 20%
Pharmacology, Toxicology and Pharmaceutical Science 3 15%
Computer Science 1 5%
Immunology and Microbiology 1 5%
Other 1 5%
Unknown 6 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 12 November 2016.
All research outputs
#1,913,000
of 8,619,738 outputs
Outputs from Malaria Journal
#788
of 3,038 outputs
Outputs of similar age
#74,262
of 243,304 outputs
Outputs of similar age from Malaria Journal
#22
of 71 outputs
Altmetric has tracked 8,619,738 research outputs across all sources so far. Compared to these this one has done well and is in the 77th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,038 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has gotten more attention than average, scoring higher than 73% 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 243,304 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 69% of its contemporaries.
We're also able to compare this research output to 71 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.