3I79

Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Toxoplasma gondii calcium-dependent protein kinase 1 is a target for selective kinase inhibitors.

Ojo, K.K.Larson, E.T.Keyloun, K.R.Castaneda, L.J.Derocher, A.E.Inampudi, K.K.Kim, J.E.Arakaki, T.L.Murphy, R.C.Zhang, L.Napuli, A.J.Maly, D.J.Verlinde, C.L.Buckner, F.S.Parsons, M.Hol, W.G.Merritt, E.A.Van Voorhis, W.C.

(2010) Nat Struct Mol Biol 17: 602-607

  • DOI: https://doi.org/10.1038/nsmb.1818
  • Primary Citation of Related Structures:  
    3I79, 3I7B, 3I7C

  • PubMed Abstract: 

    New drugs are needed to treat toxoplasmosis. Toxoplasma gondii calcium-dependent protein kinases (TgCDPKs) are attractive targets because they are absent in mammals. We show that TgCDPK1 is inhibited by low nanomolar levels of bumped kinase inhibitors (BKIs), compounds inactive against mammalian kinases. Cocrystal structures of TgCDPK1 with BKIs confirm that the structural basis for selectivity is due to the unique glycine gatekeeper residue in the ATP-binding site. We show that BKIs interfere with an early step in T. gondii infection of human cells in culture. Furthermore, we show that TgCDPK1 is the in vivo target of BKIs because T. gondii expressing a glycine to methionine gatekeeper mutant enzyme show significantly decreased sensitivity to BKIs. Thus, design of selective TgCDPK1 inhibitors with low host toxicity may be achievable.


  • Organizational Affiliation

    Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Calmodulin-domain protein kinase 1484Toxoplasma gondiiMutation(s): 0 
Gene Names: CDPK1
EC: 2.7.11.17
UniProt
Find proteins for Q9BJF5 (Toxoplasma gondii)
Explore Q9BJF5 
Go to UniProtKB:  Q9BJF5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BJF5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
EDO
Query on EDO

Download Ideal Coordinates CCD File 
B [auth A]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.04 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.144α = 90
b = 71.861β = 102.98
c = 67.265γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
SOLVEphasing
RESOLVEphasing
REFMACrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-08-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2014-11-12
    Changes: Database references
  • Version 1.3: 2017-11-01
    Changes: Refinement description
  • Version 1.4: 2024-02-21
    Changes: Data collection, Database references, Derived calculations