2PE2

CRYSTAL STRUCTURE OF HUMAN PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1 (PDK1) 3-{5-[2-Oxo-5-ureido-1,2-dihydro-indol-(3Z)-ylidenemethyl]-1H-pyrrol-3-yl}-N-(2-piperidin-1-yl-ethyl)-benzamide COMPLEX


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.13 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: Optimization of BX-517.

Islam, I.Brown, G.Bryant, J.Hrvatin, P.Kochanny, M.J.Phillips, G.B.Yuan, S.Adler, M.Whitlow, M.Lentz, D.Polokoff, M.A.Wu, J.Shen, J.Walters, J.Ho, E.Subramanyam, B.Zhu, D.Feldman, R.I.Arnaiz, D.O.

(2007) Bioorg Med Chem Lett 17: 3819-3825

  • DOI: https://doi.org/10.1016/j.bmcl.2007.05.060
  • Primary Citation of Related Structures:  
    2PE2

  • PubMed Abstract: 

    Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds.


  • Organizational Affiliation

    Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA. imadulislam@yahoo.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
3-phosphoinositide-dependent protein kinase 1286Homo sapiensMutation(s): 1 
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 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
464
Query on 464

Download Ideal Coordinates CCD File 
E [auth A]3-[5-({5-[(AMINOCARBONYL)AMINO]-2-OXO-2H-INDOL-3-YL}METHYL)-1H-PYRROL-3-YL]-N-(2-PIPERIDIN-1-YLETHYL)BENZAMIDE
C28 H30 N6 O3
PWZOBKJHPWISGC-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A],
D [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [auth A]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
A
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Binding Affinity Annotations 
IDSourceBinding Affinity
464 PDBBind:  2PE2 IC50: 4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.13 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.188 
  • R-Value Observed: 0.189 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 123.223α = 90
b = 123.223β = 90
c = 47.386γ = 120
Software Package:
Software NamePurpose
CNXrefinement
XTALVIEWrefinement
X-GENdata reduction
X-GENdata scaling
X-PLORphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-06-19
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance