5KHX

Crystal structure of JAK1 in complex with PF-4950736

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.173 

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This is version 1.1 of the entry. See complete history. 


Literature

Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system.

Caspers, N.L., Han, S., Rajamohan, F., Hoth, L.R., Geoghegan, K.F., Subashi, T.A., Vazquez, M.L., Kaila, N., Cronin, C.N., Johnson, E., Kurumbail, R.G.

(2016) Acta Crystallogr F Struct Biol Commun 72: 840-845

  • DOI: https://doi.org/10.1107/S2053230X16016356
  • Primary Citation of Related Structures:  
    5KHW, 5KHX

  • PubMed Abstract: 

    Crystals of phosphorylated JAK1 kinase domain were initially generated in complex with nucleotide (ADP) and magnesium. The tightly bound Mg 2+ -ADP at the ATP-binding site proved recalcitrant to ligand displacement. Addition of a molar excess of EDTA helped to dislodge the divalent metal ion, promoting the release of ADP and allowing facile exchange with ATP-competitive small-molecule ligands. Many kinases require the presence of a stabilizing ligand in the ATP site for crystallization. This procedure could be useful for developing co-crystallization systems with an exchangeable ligand to enable structure-based drug design of other protein kinases.

    • Organizational Affiliation: 

    Structural Biology, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase JAK1316Homo sapiensMutation(s): 0 
Gene Names: JAK1, JAK1A, JAK1B
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P23458 (Homo sapiens)
Explore P23458 
Go to UniProtKB:  P23458
PHAROS:  P23458
GTEx:  ENSG00000162434 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23458
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
6TE
Query on 6TE
Download Ideal Coordinates CCD File 
B [auth A]~{N}-[3-[methyl(7~{H}-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl]methanesulfonamide
C12 H17 N5 O2 S
QZOGHNDWZHFIJP-DTORHVGOSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
6TE BindingDB:  5KHX IC50: min: 90, max: 750 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.170 
  • R-Value Observed: 0.173 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.25α = 90
b = 88.3β = 90
c = 146.84γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
SCALAdata scaling
BUSTERphasing

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: 2016-11-09
    Type: Initial release
  • Version 1.1: 2018-05-16
    Changes: Data collection, Database references, Derived calculations