3QUP

Inhibitor bound structure of the kinase domain of the murine receptor tyrosine kinase TYRO3 (Sky)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.239 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Novel and selective spiroindoline-based inhibitors of sky kinase.

Powell, N.A.Kohrt, J.T.Filipski, K.J.Kaufman, M.Sheehan, D.Edmunds, J.E.Delaney, A.Wang, Y.Bourbonais, F.Lee, D.Y.Schwende, F.Sun, F.McConnell, P.Catana, C.Chen, H.Ohren, J.Perrin, L.A.

(2012) Bioorg Med Chem Lett 22: 190-193

  • DOI: https://doi.org/10.1016/j.bmcl.2011.11.036
  • Primary Citation of Related Structures:  
    3QUP

  • PubMed Abstract: 

    We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall.


  • Organizational Affiliation

    Pfizer Global Research & Development, Michigan Laboratories, Ann Arbor, MI 48105, USA. napowell@comcast.net


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase receptor TYRO3323Mus musculusMutation(s): 0 
Gene Names: Tyro3DtkRse
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P55144 (Mus musculus)
Explore P55144 
Go to UniProtKB:  P55144
IMPC:  MGI:104294
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP55144
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
LUN
Query on LUN

Download Ideal Coordinates CCD File 
B [auth A](5-fluoro-1H-indol-2-yl)[(3R)-1'-[(3R)-piperidin-3-yl]spiro[indole-3,3'-pyrrolidin]-1(2H)-yl]methanone
C25 H27 F N4 O
ABNVVKAVWJYHCL-KBMIEXCESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
LUN PDBBind:  3QUP IC50: 476 (nM) from 1 assay(s)
Binding MOAD:  3QUP IC50: 476 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.239 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.986α = 90
b = 57.343β = 100.3
c = 60.562γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-12-21 
  • Deposition Author(s): Ohren, J.F.

Revision History  (Full details and data files)

  • Version 1.0: 2011-12-21
    Type: Initial release
  • Version 1.1: 2012-01-11
    Changes: Database references
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations