5AV3

Crystal structure of DAPK1-kaempferol complex in the presence of iodide ions.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.185 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural Insight into the Interactions between Death-Associated Protein Kinase 1 and Natural Flavonoids.

Yokoyama, T.Kosaka, Y.Mizuguchi, M.

(2015) J Med Chem 58: 7400-7408

  • DOI: https://doi.org/10.1021/acs.jmedchem.5b00893
  • Primary Citation of Related Structures:  
    5AUT, 5AUU, 5AUV, 5AUW, 5AUX, 5AUY, 5AUZ, 5AV0, 5AV1, 5AV2, 5AV3, 5AV4

  • PubMed Abstract: 

    Death-associated protein kinase 1 (DAPK1) is a 160 kDa serine/threonine protein kinase that belongs to the Ca(2+)/calmodulin-dependent protein kinase subfamily. DAPK1 is a possible target for the treatment of acute ischemic stroke and endometrial adenocarcinomas. In the present study, we investigated the binding characteristics of 17 natural flavonoids to DAPK1 using a 1-anilinonaphthalene-8-sulfonic acid competitive binding assay and revealed that morin was the strongest binder among the selected compounds. The crystallographic analysis of DAPK1 and 7 selected flavonoid complexes revealed the structure-binding affinity relationship in atomic-level detail. It was suggested that the high affinity of morin could be accounted for by the ionic interaction between 2'-OH and K42 and that such an interaction would not take place with either cyclin-dependent protein kinases or PIM kinases because of their broader entrance regions. Thus, morin would be a more selective inhibitor of DAPK1 than either of these other types of kinases. In addition, we found that the binding of kaempferol to DAPK1 was associated with a chloride ion. The present study provides a better understanding of the molecular properties of the ATP site of DAPK1 and may be useful for the design of specific DAPK1 inhibitors.


  • Organizational Affiliation

    Faculty of Pharmaceutical Sciences, University of Toyama , 2630 Sugitani, Toyama 930-0914, 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
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
KMP
Query on KMP

Download Ideal Coordinates CCD File 
B [auth A]3,5,7-TRIHYDROXY-2-(4-HYDROXYPHENYL)-4H-CHROMEN-4-ONE
C15 H10 O6
IYRMWMYZSQPJKC-UHFFFAOYSA-N
IOD
Query on IOD

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A]
IODIDE ION
I
XMBWDFGMSWQBCA-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
KMP BindingDB:  5AV3 IC50: 1.00e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.185 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.884α = 90
b = 62.357β = 90
c = 88.329γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
Cootmodel building

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-10-07
    Type: Initial release
  • Version 1.1: 2020-02-19
    Changes: Advisory, Data collection, Database references, Derived calculations, Source and taxonomy, Structure summary
  • Version 1.2: 2024-03-20
    Changes: Data collection, Database references