PDBsum entry 2w4k

Transferase

PDB id: 2w4k

Contents

Protein chain

301 a.a. *

Ligands

ADP

Metals

_MG

Waters ×271

* Residue conservation analysis

PDB id:

2w4k

Name:

Transferase

Title:

X-ray structure of a dap-kinase 2-302

Structure:

Death-associated protein kinase 1. Chain: a. Fragment: catalytic autoinhibitory domain, residues 1-302. Synonym: death associated protein kinase i dapk, dap kinase 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

1.90Å R-factor: 0.195 R-free: 0.228

Authors:

I.De Diego,J.Kuper,F.Lehmann,M.Wilmanns

Key ref:

K.Temmerman et al. (2014). A PEF/Y substrate recognition and signature motif plays a critical role in DAPK-related kinase activity. Chem Biol, 21, 264-273. PubMed id: 24440081 DOI: 10.1016/j.chembiol.2013.12.008

Date:

27-Nov-08 Release date: 22-Dec-09

Protein chain

P53355  (DAPK1_HUMAN) -  Death-associated protein kinase 1 from Homo sapiens

Seq: 1430 a.a.

Struc: 301 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.chembiol.2013.12.008

Chem Biol 21:264-273 (2014)

PubMed id: 24440081

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

K.Temmerman, I.de Diego, V.Pogenberg, B.Simon, W.Jonko, X.Li, M.Wilmanns.

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.