4b4l
CRYSTAL STRUCTURE OF AN ARD DAP-KINASE 1 MUTANTCRYSTAL STRUCTURE OF AN ARD DAP-KINASE 1 MUTANT
Structural highlights
Publication Abstract from PubMedKnowledge 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. A PEF/Y Substrate Recognition and Signature Motif Plays a Critical Role in DAPK-Related Kinase Activity.,Temmerman K, de Diego I, Pogenberg V, Simon B, Jonko W, Li X, Wilmanns M Chem Biol. 2014 Jan 14. pii: S1074-5521(13)00457-2. doi:, 10.1016/j.chembiol.2013.12.008. PMID:24440081[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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