2XUU

Crystal structure of a DAP-kinase 1 mutant

Summary for 2XUU

• Entry DOI: 10.2210/pdb2xuu/pdb
• Related: 1IG1 1JKK 1JKL 1JKS 1JKT 1P4F 2W4J 2W4K 2X0G 2XZS 2Y0A 2Y4P 2Y4V 2YAK 3ZXT 4B4L
• Descriptor: DEATH-ASSOCIATED PROTEIN KINASE 1, ADENOSINE-5'-DIPHOSPHATE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: transferase, atp-binding, apoptosis
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Isoform 1: Cytoplasm. Isoform 2: Cytoplasm: P53355
• Total number of polymer chains: 1
• Total formula weight: 39135.75

Authors

de Diego, I.,Kuper, J.,Lehmann, F.,Wilmanns, M. (deposition date: 2010-10-21, release date: 2011-11-02, Last modification date: 2023-12-20)

Primary citation

Temmerman, K.,De Diego, I.,Pogenberg, V.,Simon, B.,Jonko, W.,Li, X.,Wilmanns, M.
A Pef/Y Substrate Recognition and Signature Motif Plays a Critical Role in Dapk-Related Kinase Activity.
Chem.Biol., 21:264-, 2014

PubMed 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.

PubMed: 24440081
DOI: 10.1016/J.CHEMBIOL.2013.12.008

Experimental method

X-RAY DIFFRACTION (1.8 Å)