3UZA

Thermostabilised Adenosine A2A receptor in complex with 6-(2,6-Dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.27 Å
  • R-Value Free: 0.335 
  • R-Value Work: 0.293 
  • R-Value Observed: 0.295 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Discovery of 1,2,4-Triazine Derivatives as Adenosine A(2A) Antagonists using Structure Based Drug Design

Congreve, M.Andrews, S.P.Dore, A.S.Hollenstein, K.Hurrell, E.Langmead, C.J.Mason, J.S.Ng, I.W.Tehan, B.Zhukov, A.Weir, M.Marshall, F.H.

(2012) J Med Chem 55: 1898-1903

  • DOI: https://doi.org/10.1021/jm201376w
  • Primary Citation of Related Structures:  
    3UZA, 3UZC

  • PubMed Abstract: 

    Potent, ligand efficient, selective, and orally efficacious 1,2,4-triazine derivatives have been identified using structure based drug design approaches as antagonists of the adenosine A(2A) receptor. The X-ray crystal structures of compounds 4e and 4g bound to the GPCR illustrate that the molecules bind deeply inside the orthosteric binding cavity. In vivo pharmacokinetic and efficacy data for compound 4k are presented, demonstrating the potential of this series of compounds for the treatment of Parkinson's disease.


  • Organizational Affiliation

    Heptares Therapeutics Limited, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK. miles.congreve@heptares.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Adenosine receptor A2a329Homo sapiensMutation(s): 8 
Gene Names: ADORA2A
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P29274 (Homo sapiens)
Explore P29274 
Go to UniProtKB:  P29274
PHAROS:  P29274
GTEx:  ENSG00000128271 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP29274
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
T4G
Query on T4G

Download Ideal Coordinates CCD File 
B [auth A]6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine
C16 H15 N5
SORFNYWLKDSNNF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
T4G BindingDB:  3UZA Ki: min: 7.76, max: 12.3 (nM) from 2 assay(s)
PDBBind:  3UZA Kd: 1.16 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.27 Å
  • R-Value Free: 0.335 
  • R-Value Work: 0.293 
  • R-Value Observed: 0.295 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 111.814α = 90
b = 111.896β = 90
c = 125.841γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
PHASERphasing
PHENIXrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-03-21
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description