6GVI

Crystal structure of PI3K alpha in complex with 3-(2-Amino-benzooxazol-5-yl)-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidine-4,6-diamine

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 

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Literature

Impact of Minor Structural Modifications on Properties of a Series of mTOR Inhibitors.

Ouvry, G., Clary, L., Tomas, L., Aurelly, M., Bonnary, L., Borde, E., Bouix-Peter, C., Chantalat, L., Defoin-Platel, C., Deret, S., Forissier, M., Harris, C.S., Isabet, T., Lamy, L., Luzy, A.P., Pascau, J., Soulet, C., Taddei, A., Taquet, N., Thoreau, E., Varvier, E., Vial, E., Hennequin, L.F.

(2019) ACS Med Chem Lett 10: 1561-1567

  • DOI: https://doi.org/10.1021/acsmedchemlett.9b00401
  • Primary Citation of Related Structures:  
    6GVF, 6GVG, 6GVH, 6GVI

  • PubMed Abstract: 

    Minor structural modifications-sometimes single atom changes-can have a dramatic impact on the properties of compounds. This is illustrated here on structures related to known mTOR inhibitor Sapanisertib. Subtle changes in the hinge binder lead to strikingly different overall profiles with changes in physical properties, metabolism, and kinase selectivity.

    • Organizational Affiliation: 

    Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform962Homo sapiensMutation(s): 0 
Gene Names: PIK3CA
EC: 2.7.1.153 (PDB Primary Data), 2.7.11.1 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P42336 (Homo sapiens)
Explore P42336 
Go to UniProtKB:  P42336
PHAROS:  P42336
GTEx:  ENSG00000121879 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP42336
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FDW
Query on FDW
Download Ideal Coordinates CCD File 
B [auth A]3-(2-azanyl-1,3-benzoxazol-5-yl)-1-propan-2-yl-pyrazolo[3,4-d]pyrimidine-4,6-diamine
C15 H16 N8 O
HGZOUPKZPOAOOQ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 59.33α = 90
b = 135.78β = 90
c = 143.15γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
MxCuBEdata collection
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-10-02
    Type: Initial release
  • Version 1.1: 2019-12-04
    Changes: Database references