1V0O

Structure of P. falciparum PfPK5-Indirubin-5-sulphonate ligand complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.233 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structures of P. Falciparum Pfpk5 Test the Cdk Regulation Paradigm and Suggest Mechanisms of Small Molecule Inhibition

Holton, S.Merckx, A.Burgess, D.Doerig, C.Noble, M.Endicott, J.

(2003) Structure 11: 1329

  • DOI: https://doi.org/10.1016/j.str.2003.09.020
  • Primary Citation of Related Structures:  
    1OB3, 1V0B, 1V0O, 1V0P

  • PubMed Abstract: 

    Plasmodium falciparum cell cycle regulators are promising targets for antimalarial drug design. We have determined the structure of PfPK5, the first structure of a P. falciparum protein kinase and the first of a cyclin-dependent kinase (CDK) not derived from humans. The fold and the mechanism of inactivation of monomeric CDKs are highly conserved across evolution. ATP-competitive CDK inhibitors have been developed as potential leads for cancer therapeutics. These studies have identified regions of the CDK active site that can be exploited to achieve significant gains in inhibitor potency and selectivity. We have cocrystallized PfPK5 with three inhibitors that target such regions. The sequence differences between PfPK5 and human CDKs within these inhibitor binding sites suggest that selective inhibition is an attainable goal. Such compounds will be useful tools for P. falciparum cell cycle studies, and will provide lead compounds for antimalarial drug development.


  • Organizational Affiliation

    Laboratory of Molecular Biophysics, Department of Biochemistry, South Parks Road, OX1 3QU, Oxford, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CELL DIVISION CONTROL PROTEIN 2 HOMOLOG
A, B
288Plasmodium falciparumMutation(s): 0 
EC: 2.7.1
UniProt
Find proteins for Q07785 (Plasmodium falciparum (isolate K1 / Thailand))
Explore Q07785 
Go to UniProtKB:  Q07785
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ07785
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
INR
Query on INR

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
2',3-DIOXO-1,1',2',3-TETRAHYDRO-2,3'-BIINDOLE-5'-SULFONIC ACID
C16 H10 N2 O5 S
IHBOEHLUIBMBMY-YPKPFQOOSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
INR PDBBind:  1V0O IC50: 5500 (nM) from 1 assay(s)
Binding MOAD:  1V0O IC50: 5500 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.233 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.562α = 90
b = 88.277β = 97.33
c = 63.857γ = 90
Software Package:
Software NamePurpose
REFMACrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-04-07
    Type: Initial release
  • Version 1.1: 2011-05-07
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance