2R7B

Crystal Structure of the Phosphoinositide-dependent Kinase-1 (PDK-1)Catalytic Domain bound to a dibenzonaphthyridine inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.225 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Discovery of Dibenzo[c,f][2,7]naphthyridines as Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 Inhibitors.

Gopalsamy, A.Shi, M.Boschelli, D.H.Williamson, R.Olland, A.M.Hu, Y.Krishnamurthy, G.Han, X.Arndt, K.Guo, B.

(2007) J Med Chem 50: 5547-5549

  • DOI: https://doi.org/10.1021/jm070851i
  • Primary Citation of Related Structures:  
    2R7B

  • PubMed Abstract: 

    With high-throughput screening, substituted dibenzo[c,f][2,7]naphthyridine 1 was identified as a novel potent and selective phosphoinositide-dependent kinase-1 (PDK-1) inhibitor. Various regions of the lead molecule were explored to understand the SAR requirement for this scaffold. The crystal structure of 1 with kinase domain of PDK-1 confirmed the binding in the active site. The key interaction of the molecule with the active site residues, observed SAR, and the biological profile are discussed in detail.


  • Organizational Affiliation

    Chemical and Screening Sciences and Oncology, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. gopalsa@wyeth.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-phosphoinositide-dependent protein kinase 1312Homo sapiensMutation(s): 0 
Gene Names: PDPK1PDK1
EC: 2.7.11.1
UniProt & NIH Common Fund Data Resources
Find proteins for O15530 (Homo sapiens)
Explore O15530 
Go to UniProtKB:  O15530
PHAROS:  O15530
GTEx:  ENSG00000140992 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO15530
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
253
Query on 253

Download Ideal Coordinates CCD File 
C [auth A]10,11-dimethoxy-4-methyldibenzo[c,f]-2,7-naphthyridine-3,6-diamine
C19 H18 N4 O2
NVINUNQBDNEMSY-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Binding Affinity Annotations 
IDSourceBinding Affinity
253 PDBBind:  2R7B IC50: 60 (nM) from 1 assay(s)
BindingDB:  2R7B IC50: 60 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.225 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.281α = 90
b = 124.281β = 90
c = 47.184γ = 120
Software Package:
Software NamePurpose
AMoREphasing
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2008-09-09 
  • Deposition Author(s): Olland, A.M.

Revision History  (Full details and data files)

  • Version 1.0: 2008-09-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 2.0: 2024-03-27
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Non-polymer description, Polymer sequence, Source and taxonomy, Structure summary