Proteomics

Dataset Information

0

Label-free quantitative analysis of PKA-dependent proteome changes in Trypanosoma brucei


ABSTRACT: Protein kinase A (PKA), the main effector of second messenger cAMP, is highly conserved among eukaryotes and a paradigm for the mechanisms of regulation of protein kinases by ligands. The unique PKA holoenzymes in the phylogenetically distant protozoan parasite Trypanosoma are unresponsive to cAMP in vitro and in vivo. By small molecule screening and optimization, we designed direct, membrane-permeable activators binding with a kD of 9 nM to the CNB pockets of the T. brucei regulatory PKA subunit. 7-Cyano-7-deazainosine has low toxicity and thus is a perfect tool to explore cAMP-independent PKA signaling in these important pathogens. This project describes the PKA-inducible proteome of the bloodstream stage of T. brucei.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Trypanosoma Brucei

SUBMITTER: Dupuy Jean-William  

LAB HEAD: Michael Boshart

PROVIDER: PXD009073 | Pride | 2019-02-25

REPOSITORIES: pride

Dataset's files

Source:
Action DRS
andromeda.zip Other
mb161104_01.raw Raw
mb161104_02.raw Raw
mb161104_03.raw Raw
mb161104_04.raw Raw
Items per page:
1 - 5 of 21
altmetric image

Publications


Protein kinase A (PKA), the main effector of cAMP in eukaryotes, is a paradigm for the mechanisms of ligand-dependent and allosteric regulation in signalling. Here we report the orthologous but cAMP-independent PKA of the protozoan Trypanosoma and identify 7-deaza-nucleosides as potent activators (EC<sub>50</sub> ≥ 6.5 nM) and high affinity ligands (K<sub>D</sub> ≥ 8 nM). A co-crystal structure of trypanosome PKA with 7-cyano-7-deazainosine and molecular docking show how substitution of key amin  ...[more]

Similar Datasets

2019-02-25 | PXD012245 | Pride
2022-08-17 | PXD025357 | Pride
2023-09-13 | PXD045088 | Pride
2014-07-01 | E-GEOD-57217 | biostudies-arrayexpress
2018-08-05 | E-MTAB-7038 | biostudies-arrayexpress
2007-08-31 | E-GEOD-2413 | biostudies-arrayexpress
2005-04-15 | GSE2413 | GEO
2017-05-27 | MSV000081115 | MassIVE
2022-10-14 | PXD032160 | Pride
2021-08-24 | GSE182498 | GEO