1E8X

STRUCTURAL INSIGHTS INTO PHOSHOINOSITIDE 3-KINASE ENZYMATIC MECHANISM AND SIGNALLING


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.255 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural Determinations of Phosphoinositide 3-Kinase Inhibition by Wortmannin, Ly294002, Quercetin, Myricetin and Staurosporine

Walker, E.H.Pacold, M.E.Perisic, O.Stephens, L.Hawkins, P.T.Whymann, M.P.Williams, R.L.

(2000) Mol Cell 6: 909

  • DOI: https://doi.org/10.1016/s1097-2765(05)00089-4
  • Primary Citation of Related Structures:  
    1E7U, 1E7V, 1E8W, 1E8X, 1E8Y, 1E8Z, 1E90

  • PubMed Abstract: 

    The specific phosphoinositide 3-kinase (PI3K) inhibitors wortmannin and LY294002 have been invaluable tools for elucidating the roles of these enzymes in signal transduction pathways. The X-ray crystallographic structures of PI3Kgamma bound to these lipid kinase inhibitors and to the broad-spectrum protein kinase inhibitors quercetin, myricetin, and staurosporine reveal how these compounds fit into the ATP binding pocket. With a nanomolar IC50, wortmannin most closely fits and fills the active site and induces a conformational change in the catalytic domain. Surprisingly, LY294002 and the lead compound on which it was designed, quercetin, as well as the closely related flavonoid myricetin bind PI3K in remarkably different orientations that are related to each other by 180 degrees rotations. Staurosporine/PI3K interactions are reminiscent of low-affinity protein kinase/staurosporine complexes. These results provide a rich basis for development of isoform-specific PI3K inhibitors with therapeutic potential.


  • Organizational Affiliation

    MRC Laboratory of Molecular Biology, MRC Centre, Cambridge, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PHOSPHATIDYLINOSITOL 3-KINASE CATALYTIC SUBUNIT961Sus scrofaMutation(s): 0 
Gene Names: P120S144C
EC: 2.7.1.137
UniProt
Find proteins for O02697 (Sus scrofa)
Explore O02697 
Go to UniProtKB:  O02697
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO02697
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ATP
Query on ATP

Download Ideal Coordinates CCD File 
B [auth A]ADENOSINE-5'-TRIPHOSPHATE
C10 H16 N5 O13 P3
ZKHQWZAMYRWXGA-KQYNXXCUSA-N
LU
Query on LU

Download Ideal Coordinates CCD File 
C [auth A]
D [auth A]
E [auth A]
F [auth A]
G [auth A]
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A]
LUTETIUM (III) ION
Lu
PSDMOPINLDTFSZ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.255 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 143.288α = 90
b = 67.561β = 95.93
c = 106.952γ = 90
Software Package:
Software NamePurpose
SOLVEmodel building
SCALAdata scaling
CNSphasing
SHARPphasing
SOLOMONphasing
SOLVEphasing
CNSrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-10-26
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-10-24
    Changes: Data collection, Source and taxonomy