5HEZ

JAK2 kinase (JH1 domain) mutant P1057A in complex with TG101209


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.66 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity.

Dendrou, C.A.Cortes, A.Shipman, L.Evans, H.G.Attfield, K.E.Jostins, L.Barber, T.Kaur, G.Kuttikkatte, S.B.Leach, O.A.Desel, C.Faergeman, S.L.Cheeseman, J.Neville, M.J.Sawcer, S.Compston, A.Johnson, A.R.Everett, C.Bell, J.I.Karpe, F.Ultsch, M.Eigenbrot, C.McVean, G.Fugger, L.

(2016) Sci Transl Med 8: 363ra149-363ra149

  • DOI: https://doi.org/10.1126/scitranslmed.aag1974
  • Primary Citation of Related Structures:  
    5HEZ

  • PubMed Abstract: 

    Thousands of genetic variants have been identified, which contribute to the development of complex diseases, but determining how to elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 (TYK2) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders; subsequent molecular, cellular, in vivo, and structural functional follow-up; and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for certain common autoimmune disorders.


  • Organizational Affiliation

    Oxford Centre for Neuroinflammation, Nuffield Department of Clinical Neurosciences, Division of Clinical Neurology, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase JAK2
A, B, C, D
302Homo sapiensMutation(s): 1 
Gene Names: JAK2
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for O60674 (Homo sapiens)
Explore O60674 
Go to UniProtKB:  O60674
PHAROS:  O60674
GTEx:  ENSG00000096968 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO60674
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
1M3
Query on 1M3

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
J [auth B]
K [auth B]
M [auth C]
G [auth A],
H [auth A],
J [auth B],
K [auth B],
M [auth C],
N [auth C],
P [auth D],
Q [auth D]
N-tert-butyl-3-[(5-methyl-2-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl)amino]benzenesulfonamide
C26 H35 N7 O2 S
JVDOKQYTTYUYDV-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
F [auth A],
L [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B],
O [auth D]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A, B, C, D
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Binding Affinity Annotations 
IDSourceBinding Affinity
1M3 BindingDB:  5HEZ IC50: 6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.66 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.218 
  • Space Group: C 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 211.813α = 90
b = 215.649β = 90
c = 91.497γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-09
    Type: Initial release
  • Version 1.1: 2016-11-16
    Changes: Derived calculations
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.3: 2023-11-15
    Changes: Data collection