6HM6

CRYSTAL STRUCTURE OF SPLEEN TYROSINE KINASE (SYK) IN COMPLEX WITH A 2-(PYRIDINYLOXYMETHYL)PYRIDINE INHIBITOR

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.217 

Starting Model: other
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease.

Barker, M.D., Liddle, J., Atkinson, F.L., Wilson, D.M., Dickson, M.C., Ramirez-Molina, C., Lewis, H., Davis, R.P., Somers, D.O., Neu, M., Jones, E., Watson, R.

(2018) Bioorg Med Chem Lett 28: 3458-3462

  • DOI: https://doi.org/10.1016/j.bmcl.2018.09.022
  • Primary Citation of Related Structures:  
    6HM6, 6HM7

  • PubMed Abstract: 

    The discovery and lead optimisation of a novel series of SYK inhibitors is described. These were optimised for SYK potency and selectivity against Aurora B. Compounds were profiled in a human skin penetration study to identify a suitable candidate molecule for pre-clinical development. Compound 44 (GSK2646264) was selected for progression and is currently in Phase I clinical trials.

    • Organizational Affiliation: 

    GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. Electronic address: [email protected].


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SPLEEN TYROSINE KINASE276Homo sapiensMutation(s): 0 
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P43405 (Homo sapiens)
Explore P43405 
Go to UniProtKB:  P43405
PHAROS:  P43405
GTEx:  ENSG00000165025 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP43405
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.290 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.217 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.437α = 90
b = 84.982β = 100.5
c = 40.277γ = 90
Software Package:
Software NamePurpose
d*TREKdata reduction
d*TREKdata scaling
PDB_EXTRACTdata extraction
REFMACphasing
REFMACrefinement
Cootmodel building

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2018-10-10 
    • Deposition Author(s): Somers, D.O.

Revision History  (Full details and data files)

  • Version 1.0: 2018-10-10
    Type: Initial release
  • Version 1.1: 2018-10-17
    Changes: Data collection, Database references
  • Version 1.2: 2024-05-01
    Changes: Data collection, Database references, Refinement description
  • Version 1.3: 2024-11-06
    Changes: Structure summary