3UZC

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

PDB DOI: https://doi.org/10.2210/pdb3UZC/pdb

Classification: SIGNALING PROTEIN
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): Yes
Membrane Protein: Yes PDBTMMemProtMD

Deposited: 2011-12-07 Released: 2012-03-21
Deposition Author(s): Congreve, M., Andrews, S.P., Dore, A.S., Hollenstein, K., Hurrell, E., Langmead, C.J., Mason, J.S., Ng, I.W., Zhukov, A., Weir, M., Marshall, F.H.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.34 Å
R-Value Free: 0.290
R-Value Work: 0.282
R-Value Observed: 0.282

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 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

PubMed: 22220592 Search on PubMedSearch on PubMed Central
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. [email protected]

Macromolecule Content

Total Structure Weight: 36.78 kDa
Atom Count: 2,271
Modelled Residue Count: 291
Deposited Residue Count: 329
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Adenosine A2A Receptor	A	329	Homo sapiens	Mutation(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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P29274
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
T4E Query on T4E Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	4-(3-amino-5-phenyl-1,2,4-triazin-6-yl)-2-chlorophenol C₁₅ H₁₁ Cl N₄ O ZHUZHTHIEMXLRA-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
T4E	BindingDB: 3UZC	Ki: min: 1.38, max: 4 (nM) from 3 assay(s)
T4E	PDBBind: 3UZC	Kd: 0.25 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.34 Å
R-Value Free: 0.290
R-Value Work: 0.282
R-Value Observed: 0.282
Space Group: I 2 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 110.7	α = 90
b = 112.064	β = 90
c = 126.9	γ = 90

Software Package:

Software Name	Purpose
XDS	data scaling
PHASER	phasing
PHENIX	refinement
XDS	data reduction
SCALA	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-03-21

Deposition Author(s):

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
Version 1.2: 2024-10-30
Changes: Structure summary