3NZ0

Non-phosphorylated TYK2 kinase with CMP6


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A new regulatory switch in a JAK protein kinase.

Tsui, V.Gibbons, P.Ultsch, M.Mortara, K.Chang, C.Blair, W.Pulk, R.Stanley, M.Starovasnik, M.Williams, D.Lamers, M.Leonard, P.Magnuson, S.Liang, J.Eigenbrot, C.

(2011) Proteins 79: 393-401

  • DOI: https://doi.org/10.1002/prot.22889
  • Primary Citation of Related Structures:  
    3NYX, 3NZ0

  • PubMed Abstract: 

    Members of the JAK family of protein kinases mediate signal transduction from cytokine receptors to transcription factor activation. Over-stimulation of these pathways is causative in immune disorders like rheumatoid arthritis, psoriasis, lupus, and Crohn's disease. A search for selective inhibitors of a JAK kinase has led to our characterization of a previously unknown kinase conformation arising from presentation of Tyr962 of TYK2 to an inhibitory small molecule via an H-bonding interaction. A small minority of protein kinase domains has a Tyrosine residue in this position within the αC-β4 loop, and it is the only amino acid commonly seen here with H-bonding potential. These discoveries will aid design of inhibitors that discriminate among the JAK family and more widely among protein kinases.


  • Organizational Affiliation

    Department of Discovery Chemistry, Genentech, Inc, South San Francisco, California 94080, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Non-receptor tyrosine-protein kinase TYK2302Homo sapiensMutation(s): 1 
Gene Names: TYK2
EC: 2.7.10.2
UniProt & NIH Common Fund Data Resources
Find proteins for P29597 (Homo sapiens)
Explore P29597 
Go to UniProtKB:  P29597
PHAROS:  P29597
GTEx:  ENSG00000105397 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29597
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IZA
Query on IZA

Download Ideal Coordinates CCD File 
B [auth A]2-TERT-BUTYL-9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLINE-7-ONE
C18 H16 F N3 O
VNDWQCSOSCCWIP-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IZA BindingDB:  3NZ0 IC50: min: 1, max: 1700 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.59α = 90
b = 64.91β = 90
c = 83.02γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
MOLREPphasing
REFMACrefinement
CrystalCleardata reduction
CrystalCleardata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-10-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description