2FUM

Catalytic domain of protein kinase PknB from Mycobacterium tuberculosis in complex with mitoxantrone


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.221 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

The structure of PknB in complex with mitoxantrone, an ATP-competitive inhibitor, suggests a mode of protein kinase regulation in mycobacteria

Wehenkel, A.Fernandez, P.Bellinzoni, M.Catherinot, V.Barilone, N.Labesse, G.Jackson, M.Alzari, P.M.

(2006) FEBS Lett 580: 3018-3022

  • DOI: https://doi.org/10.1016/j.febslet.2006.04.046
  • Primary Citation of Related Structures:  
    2FUM

  • PubMed Abstract: 

    Mycobacterium tuberculosis PknB is an essential receptor-like protein kinase involved in cell growth control. Here, we demonstrate that mitoxantrone, an anthraquinone derivative used in cancer therapy, is a PknB inhibitor capable of preventing mycobacterial growth. The structure of the complex reveals that mitoxantrone partially occupies the adenine-binding pocket in PknB, providing a framework for the design of compounds with potential therapeutic applications. PknB crystallizes as a 'back-to-back' homodimer identical to those observed in other structures of PknB in complex with ATP analogs. This organization resembles that of the RNA-dependent protein kinase PKR, suggesting a mechanism for kinase activation in mycobacteria.


  • Organizational Affiliation

    Unité de Biochimie Structurale and CNRS URA2185, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Probable serine/threonine-protein kinase pknB
A, B, C, D
299Mycobacterium tuberculosis H37RvMutation(s): 0 
Gene Names: pknB
EC: 2.7.1.37
UniProt
Find proteins for P9WI81 (Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv))
Explore P9WI81 
Go to UniProtKB:  P9WI81
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP9WI81
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
MIX PDBBind:  2FUM IC50: 800 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.218 
  • R-Value Observed: 0.221 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 116.863α = 90
b = 116.863β = 90
c = 260.347γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
CCP4data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-08-01
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary