3QC4

PDK1 in complex with DFG-OUT inhibitor xxx

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history. 


Literature

Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.

Erlanson, D.A., Arndt, J.W., Cancilla, M.T., Cao, K., Elling, R.A., English, N., Friedman, J., Hansen, S.K., Hession, C., Joseph, I., Kumaravel, G., Lee, W.C., Lind, K.E., McDowell, R.S., Miatkowski, K., Nguyen, C., Nguyen, T.B., Park, S., Pathan, N., Penny, D.M., Romanowski, M.J., Scott, D., Silvian, L., Simmons, R.L., Tangonan, B.T., Yang, W., Sun, L.

(2011) Bioorg Med Chem Lett 21: 3078-3083

  • DOI: https://doi.org/10.1016/j.bmcl.2011.03.032
  • Primary Citation of Related Structures:  
    3PWY, 3QC4

  • PubMed Abstract: 

    We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the 'DFG-out' conformation.

    • Organizational Affiliation: 

    Sunesis Pharmaceuticals, Inc., 395 Oyster Point Blvd., South San Francisco, CA 94080, USA. derlanson@carmot.us


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-phosphoinositide-dependent protein kinase 1
A, B
314Homo sapiensMutation(s): 2 
Gene Names: PDPK1, PDK1
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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MP7
Query on MP7
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		1-(3,4-difluorobenzyl)-2-oxo-N-{(1R)-2-[(2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)oxy]-1-phenylethyl}-1,2-dihydropyridine-3-carboxamide
C28 H22 F2 N4 O4
GCWCGSPBENFEPE-VWLOTQADSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A, B
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Binding Affinity Annotations 
IDSourceBinding Affinity
MP7 PDBBind:  3QC4 IC50: 2 (nM) from 1 assay(s)
Binding MOAD:  3QC4 IC50: 2 (nM) from 1 assay(s)
BindingDB:  3QC4 IC50: 500 (nM) from 1 assay(s)
EC50: 1 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 183.147α = 90
b = 57.336β = 114.13
c = 83.694γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2011-04-20 
    • Deposition Author(s): Arndt, J.W.

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance