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PDBsum entry 2w4k
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References listed in PDB file
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Key reference
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Title
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A pef/y substrate recognition and signature motif plays a critical role in dapk-Related kinase activity.
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Authors
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K.Temmerman,
I.De diego,
V.Pogenberg,
B.Simon,
W.Jonko,
X.Li,
M.Wilmanns.
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Ref.
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Chem Biol, 2014,
21,
264-273.
[DOI no: ]
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PubMed id
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Abstract
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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.
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