1P4F

DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury.

Velentza, A.V.Wainwright, M.S.Zasadzki, M.Mirzoeva, S.Schumacher, A.M.Haiech, J.Focia, P.J.Egli, M.Watterson, D.M.

(2003) Bioorg Med Chem Lett 13: 3465-3470

  • DOI: https://doi.org/10.1016/s0960-894x(03)00733-9
  • Primary Citation of Related Structures:  
    1P4F

  • PubMed Abstract: 

    Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury attenuated brain tissue or neuronal biomarker loss measured, respectively, 1 week and 3 days later. Because aminopyridazine is a privileged structure in neuropharmacology, we determined the high-resolution crystal structure of a binary complex between the kinase domain and a molecular fragment of the DAPK inhibitor. The co-crystal structure describes a structural basis for interaction and provides a firm foundation for structure-assisted design of lead compounds with appropriate molecular properties for future drug development.


  • Organizational Affiliation

    Drug Discovery Program, Northwestern University, 303 E. Chicago Avenue, Ward 8-196, Chicago, IL 60611, USA.


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: DAPK1 OR DAPK
EC: 2.7.1
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
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
86Q
Query on 86Q

Download Ideal Coordinates CCD File 
B [auth A]5,6-Dihydro-benzo[H]cinnolin-3-ylamine
C12 H11 N3
QKVREUJWFZJEJK-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.238α = 90
b = 62.527β = 90
c = 88.927γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
SCALEPACKdata scaling
CNSrefinement
CNSphasing
MAR345data collection

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-09-28
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Advisory, Refinement description
  • Version 1.4: 2019-07-24
    Changes: Data collection, Refinement description
  • Version 2.0: 2021-09-15
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary
  • Version 2.1: 2023-08-16
    Changes: Data collection, Refinement description