Paper Citing NAMD - Abstract
Temmerman, Koen; de Diego, Inaki; Pogenberg, Vivian; Simon, Bertrand; Jonko, Weronika; Li, Xun; Wilmanns, Matthias
A PEF/Y Substrate Recognition and Signature Motif Plays a Critical Role in DAPK-Related Kinase Activity
CHEMISTRY & BIOLOGY, 21:264-273, FEB 20 2014
Knowledge about protein kinase substrate preferences is biased toward residues immediately adjacent to the site of phosphorylation. By a combined structural, biochemical, and cellular approach, we have discovered an unexpected substrate recognition element with the consensus sequence PEF/Y in the tumor suppressor death-associated protein kinase 1. This motif can be effectively blocked by a specific pseudosubstrate-type interaction with an autoregulatory domain of this kinase. In this arrangement, the central PEF/Y glutamate interacts with a conserved arginine distant to the phosphorylation site in sequence and structure. We also demonstrate that the element is crucial for kinase activity regulation and substrate recognition. The PEF/Y motif distinguishes close death-associated protein kinase relatives from canonical calcium/calmodulin-dependent protein kinases. Insight into this signature and mode of action offers new opportunities to identify specific small molecule inhibitors in PEF/Y-containing protein kinases.
