4M84

Calcium-Dependent Protein Kinase 1 from Toxoplasma gondii (TgCDPK1) in complex with inhibitor UW1455


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 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: AAG53993CDPK1TGGT1_059880TGVEG_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
21E
Query on 21E

Download Ideal Coordinates CCD File 
B [auth A]5-amino-1-tert-butyl-3-(quinolin-2-yl)-1H-pyrazole-4-carboxamide
C17 H19 N5 O
YKVANMRHVMVLJX-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
21E Binding MOAD:  4M84 IC50: 49 (nM) from 1 assay(s)
BindingDB:  4M84 IC50: 49 (nM) from 1 assay(s)
PDBBind:  4M84 IC50: 49 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.201 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.12α = 90
b = 73.18β = 99.77
c = 66.01γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
MOSFLMdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-02
    Type: Initial release
  • Version 1.1: 2014-02-05
    Changes: Database references
  • Version 1.2: 2014-03-05
    Changes: Database references
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description