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STK32A is a dual-specificity AGC kinase with a preference for acidic substrates

Authors :
Stefan Knapp
F.J. Sorrell
Apirat Chaikuad
K. R. Abdul Azeez
Arminja N. Kettenbach
Scott A. Gerber
F. Miranda
Ahmed Ashour Ahmed
Jonathan M. Elkins
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

The STK32 kinases are a small subfamily of three uncharacterised serine/threonine kinases from the AGC kinase family whose functional role is so far unknown. Here, we analyse the consensus peptide sequence for STK32A phosphorylation, showing that STK32A is directed towards acidic substrate sequences and exhibits dual-specificity for serine/threonine and tyrosine residues. A crystal structure of STK32A reveals an overall structure typical of the AGC protein kinase family but with significant and unique features including an altered binding mode of the hydrophobic motif to the N-terminal lobe of the kinase domain, and a novel alpha-helix in between the turn motif and the hydrophobic motif. The crystal structure combined with phylogenetic analysis reveals the evolutionary conservation of the acidic substrate preference.In vitrobinding assays demonstrated that the STK32 kinases bind significant numbers of clinically used kinase inhibitors.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....8b338a10cc51886c6414c56cbfb0f3de
Full Text :
https://doi.org/10.1101/2020.03.04.976555