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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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A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity. / Temmerman, Koen; de Diego, Iñaki; Pogenberg, Vivian; Simon, Bertrand; Jonko, Weronika; Li, Xun; Wilmanns, Matthias.

In: CHEM BIOL, Vol. 21, No. 2, 20.02.2014, p. 264-73.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Temmerman, K, de Diego, I, Pogenberg, V, Simon, B, Jonko, W, Li, X & Wilmanns, M 2014, 'A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity', CHEM BIOL, vol. 21, no. 2, pp. 264-73. https://doi.org/10.1016/j.chembiol.2013.12.008

APA

Temmerman, K., de Diego, I., Pogenberg, V., Simon, B., Jonko, W., Li, X., & Wilmanns, M. (2014). A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity. CHEM BIOL, 21(2), 264-73. https://doi.org/10.1016/j.chembiol.2013.12.008

Vancouver

Temmerman K, de Diego I, Pogenberg V, Simon B, Jonko W, Li X et al. A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity. CHEM BIOL. 2014 Feb 20;21(2):264-73. https://doi.org/10.1016/j.chembiol.2013.12.008

Bibtex

@article{ac2d5c91c3ff4c8e8470b468325ca4b5,
title = "A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity",
abstract = "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. ",
keywords = "Amino Acid Sequence, Amino Acid Substitution, Binding Sites, Crystallography, X-Ray, Death-Associated Protein Kinases/chemistry, HEK293 Cells, Humans, Molecular Docking Simulation, Molecular Sequence Data, Peptides/chemistry, Protein Structure, Tertiary, Sequence Alignment, Substrate Specificity",
author = "Koen Temmerman and {de Diego}, I{\~n}aki and Vivian Pogenberg and Bertrand Simon and Weronika Jonko and Xun Li and Matthias Wilmanns",
note = "Copyright {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",
year = "2014",
month = feb,
day = "20",
doi = "10.1016/j.chembiol.2013.12.008",
language = "English",
volume = "21",
pages = "264--73",
number = "2",

}

RIS

TY - JOUR

T1 - A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity

AU - Temmerman, Koen

AU - de Diego, Iñaki

AU - Pogenberg, Vivian

AU - Simon, Bertrand

AU - Jonko, Weronika

AU - Li, Xun

AU - Wilmanns, Matthias

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/2/20

Y1 - 2014/2/20

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Amino Acid Substitution

KW - Binding Sites

KW - Crystallography, X-Ray

KW - Death-Associated Protein Kinases/chemistry

KW - HEK293 Cells

KW - Humans

KW - Molecular Docking Simulation

KW - Molecular Sequence Data

KW - Peptides/chemistry

KW - Protein Structure, Tertiary

KW - Sequence Alignment

KW - Substrate Specificity

U2 - 10.1016/j.chembiol.2013.12.008

DO - 10.1016/j.chembiol.2013.12.008

M3 - SCORING: Journal article

C2 - 24440081

VL - 21

SP - 264

EP - 273

IS - 2

ER -