4ONA

Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1517

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history. 


Literature

Potent and selective inhibitors of CDPK1 from T. gondii and C. parvum based on a 5-aminopyrazole-4-carboxamide scaffold.

Zhang, Z., Ojo, K.K., Vidadala, R., Huang, W., Geiger, J.A., Scheele, S., Choi, R., Reid, M.C., Keyloun, K.R., Rivas, K., Siddaramaiah, L.K., Comess, K.M., Robinson, K.P., Merta, P.J., Kifle, L., Hol, W.G., Parsons, M., Merritt, E.A., Maly, D.J., Verlinde, C.L., Van Voorhis, W.C., Fan, E.

(2014) ACS Med Chem Lett 5: 40-44

  • DOI: https://doi.org/10.1021/ml400315s
  • Primary Citation of Related Structures:  
    4M84, 4ONA

  • PubMed Abstract: 

    5-Aminopyrazole-4-carboxamide was used as an alternative scaffold to substitute for the pyrazolopyrimidine of a known "bumped kinase inhibitor" to create selective inhibitors of calcium-dependent protein kinase-1 from both Toxoplasma gondii and Cryptosporidium parvum . Compounds with low nanomolar inhibitory potencies against the target enzymes were obtained. The most selective inhibitors also exhibited submicromolar activities in T. gondii cell proliferation assays and were shown to be non-toxic to mammalian cells.

    • Organizational Affiliation: 

    Department of Biochemistry, University of Washington, Seattle, WA 98195, United States.


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: AAG53993, CDPK1, TGVEG_042030
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
UW1
Query on UW1
Download Ideal Coordinates CCD File 
B [auth A]5-amino-1-tert-butyl-3-(7-ethoxyquinolin-3-yl)-1H-pyrazole-4-carboxamide
C19 H23 N5 O2
XZLFLNWUBLMFQW-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
UW1 BindingDB:  4ONA IC50: 2 (nM) from 1 assay(s)
Binding MOAD:  4ONA IC50: 2 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.190 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.27α = 90
b = 72.631β = 102.36
c = 67.2γ = 90
Software Package:
Software NamePurpose
Aimlessdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
MOSFLMdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-03-19
    Type: Initial release
  • Version 1.1: 2014-09-24
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description