5E91

TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN (E431A,R433A,E485A,K488A,R493A,R495A) IN COMPLEX WITH 3-AMINO-6-[4-(2- HYDROXYETHYL)PHENYL]-N-[4-(MORPHOLIN-4-YL)PYRIDIN-3-YL] PYRAZINE-2-CARBOXAMIDE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Crystal structures of apo and inhibitor-bound TGF beta R2 kinase domain: insights into TGF beta R isoform selectivity.

Tebben, A.J.Ruzanov, M.Gao, M.Xie, D.Kiefer, S.E.Yan, C.Newitt, J.A.Zhang, L.Kim, K.Lu, H.Kopcho, L.M.Sheriff, S.

(2016) Acta Crystallogr D Struct Biol 72: 658-674

  • DOI: https://doi.org/10.1107/S2059798316003624
  • Primary Citation of Related Structures:  
    5E8S, 5E8T, 5E8U, 5E8V, 5E8W, 5E8X, 5E8Y, 5E8Z, 5E90, 5E91, 5E92

  • PubMed Abstract: 

    The cytokine TGF-β modulates a number of cellular activities and plays a critical role in development, hemostasis and physiology, as well as in diseases including cancer and fibrosis. TGF-β signals through two transmembrane serine/threonine kinase receptors: TGFβR1 and TGFβR2. Multiple structures of the TGFβR1 kinase domain are known, but the structure of TGFβR2 remains unreported. Wild-type TGFβR2 kinase domain was refractory to crystallization, leading to the design of two mutated constructs: firstly, a TGFβR1 chimeric protein with seven ATP-site residues mutated to their counterparts in TGFβR2, and secondly, a reduction of surface entropy through mutation of six charged residues on the surface of the TGFβR2 kinase domain to alanines. These yielded apo and inhibitor-bound crystals that diffracted to high resolution (<2 Å). Comparison of these structures with those of TGFβR1 reveal shared ligand contacts as well as differences in the ATP-binding sites, suggesting strategies for the design of pan and selective TGFβR inhibitors.


  • Organizational Affiliation

    Molecular Structure and Design, Bristol-Myers Squibb R & D, PO Box 4000, Princeton, NJ 08543-4000, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TGF-beta receptor type-2316Homo sapiensMutation(s): 6 
Gene Names: TGFBR2
EC: 2.7.11.30
UniProt & NIH Common Fund Data Resources
Find proteins for P37173 (Homo sapiens)
Explore P37173 
Go to UniProtKB:  P37173
PHAROS:  P37173
GTEx:  ENSG00000163513 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP37173
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5L4
Query on 5L4

Download Ideal Coordinates CCD File 
B [auth A]3-amino-6-[4-(2-hydroxyethyl)phenyl]-N-[4-(morpholin-4-yl)pyridin-3-yl]pyrazine-2-carboxamide
C22 H24 N6 O3
UEECNVFACUZGKV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.42 Å
  • R-Value Free: 0.242 
  • R-Value Work: 0.208 
  • R-Value Observed: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.86α = 90
b = 75.77β = 90
c = 75.07γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
Aimlessdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2016-05-11 
  • Deposition Author(s): Sheriff, S.

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-11
    Type: Initial release
  • Version 1.1: 2018-04-18
    Changes: Data collection, Database references, Derived calculations
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Refinement description