Evidence map›Paper›PMID 23530747›Full record

ArticleACS chemical biology2013

Exploiting the unique ATP-binding pocket of toxoplasma calcium-dependent protein kinase 1 to identify its substrates.

Sebastian Lourido, Grace R Jeschke, Benjamin E Turk, L David Sibley

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.6field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 59 citations in OpenAlex.

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  14. Protein kinases in Toxoplasma gondii.International journal for parasitology · 2021
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Sebastian LouridoDepartment of Molecular Microbiology, Washington University School of Medicine , 660 S. Euclid Ave., St. Louis, Missouri 63110, United States.
Grace R Jeschke
Benjamin E Turk
L David Sibley
Washington University in St. Louis · USYale University · US

Funding

PROTEIN SECRETION &INTRACELLULAR SURVIVAL BY TOXOPLASMAR01AI034036 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 1993 to 2019
$7.9M
DESIGNING SELECTIVE INHIBITORS OF CALCIUM-DEPENDENT KINASES IN PARASITESR01AI094098 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 2012 to 2015
$1.6M
NIAID NIH HHS AI034036NIAID NIH HHS R01 AI034036NIAID NIH HHS R01 AI094098
6 · The paper itself

Abstract

Apicomplexan parasites rely on calcium as a second messenger to regulate a variety of essential cellular processes. Calcium-dependent protein kinases (CDPK), which transduce these signals, are conserved among apicomplexans but absent from mammalian hosts, making them attractive targets for therapeutic intervention. Despite their importance, the signaling pathways CDPK regulate remain poorly characterized, and their protein substrates are completely unknown. In Toxoplasma gondii, CDPK1 is required for calcium-regulated secretion from micronemes, thereby controlling motility, invasion, and egress from host cells. CDPK1 is unique among parasite and mammalian kinases in containing glycine at the key "gatekeeper" residue, which results in an expanded ATP-binding pocket. In the present study, we use a synthetic ATPγS analogue that displays steric complementarity to the ATP-binding pocket and hence allows identification of protein substrates based on selective thiophosphorylation. The specificity of this approach was validated by the concordance between the identified phosphorylation sites and the in vitro substrate preference of CDPK1. We further demonstrate that the phosphorylation of predicted substrates is dependent on CDPK1 both in vivo and in vitro. This combined strategy for identifying the targets of specific protein kinases provides a platform for defining the roles of CDPKs in apicomplexans.

Indexed as

Adenosine TriphosphateAmino Acid SequenceBinding SitesCalcium-Calmodulin-Dependent Protein KinasesHumansMolecular Sequence DataPeptidesPhosphatesPhosphorylationProtein KinasesSubstrate SpecificityToxoplasmaToxoplasmosisAdenosine TriphosphateCalcium-Calmodulin-Dependent Protein KinasesPeptidesPhosphatesProtein Kinasesthiophosphoric acid

Identifiers

PMID23530747
PMCPMC3691715
OpenAlexW2121008880

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.