8IE6

Crystal structure of DAPK1 in complex with pinostilbene


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 

Starting Model: experimental
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This is version 1.1 of the entry. See complete history


Literature

Characterization of the molecular interactions between resveratrol derivatives and death-associated protein kinase 1.

Yokoyama, T.Kusaka, K.

(2023) FEBS J 290: 4465-4479

  • DOI: https://doi.org/10.1111/febs.16817
  • Primary Citation of Related Structures:  
    8IE5, 8IE6, 8IE7, 8IE8

  • PubMed Abstract: 

    Death-associated protein kinase 1 (DAPK1), a Ca2+/calmodulin-regulated serine/threonine kinase, regulates cell apoptosis and autophagy and has been implicated in the pathogenesis of Alzheimer's disease (AD). Targeting DAPK1 may be a promising approach for treating AD. In our previous study, we found that a natural polyphenol, resveratrol (1), is a moderate DAPK1 inhibitor. In the present study, we investigated the interactions between natural and synthetic derivatives of 1 and DAPK1. Binding assays including intrinsic fluorescence quenching, protein thermal shift and isothermal titration calorimetry indicated that oxyresveratrol (3), a hydroxylated derivative, and pinostilbene (5), a methoxylated derivative, bind to DAPK1 with comparable affinity to 1. The enzymatic assay showed that 3 more effectively inhibits the intrinsic ATPase activity of DAPK1 compared with 1. Crystallographic analysis revealed that the binding modes of the methoxylated derivatives were different from those of 1 and 3, resulting in a unique interaction. Our results suggest that 3 may be helpful in treating AD and provide a clue for the development of promising DAPK1 inhibitors.


  • Organizational Affiliation

    Faculty of Pharmaceutical Sciences, University of Toyama, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Death-associated protein kinase 1293Homo sapiensMutation(s): 0 
Gene Names: DAPK1DAPK
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for P53355 (Homo sapiens)
Explore P53355 
Go to UniProtKB:  P53355
PHAROS:  P53355
GTEx:  ENSG00000196730 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP53355
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.179 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.719α = 90
b = 62.233β = 90
c = 88.418γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data

  • Released Date: 2023-05-24 
  • Deposition Author(s): Yokoyama, T.

Funding OrganizationLocationGrant Number
Not funded--

Revision History  (Full details and data files)

  • Version 1.0: 2023-05-24
    Type: Initial release
  • Version 1.1: 2023-10-04
    Changes: Data collection, Database references