3EML

The 2.6 A Crystal Structure of a Human A2A Adenosine Receptor bound to ZM241385.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 

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Ligand Structure Quality Assessment 


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Literature

The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist.

Jaakola, V.P.Griffith, M.T.Hanson, M.A.Cherezov, V.Chien, E.Y.Lane, J.R.Ijzerman, A.P.Stevens, R.C.

(2008) Science 322: 1211-1217

  • DOI: https://doi.org/10.1126/science.1164772
  • Primary Citation of Related Structures:  
    3EML

  • PubMed Abstract: 

    The adenosine class of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) mediates the important role of extracellular adenosine in many physiological processes and is antagonized by caffeine. We have determined the crystal structure of the human A2A adenosine receptor, in complex with a high-affinity subtype-selective antagonist, ZM241385, to 2.6 angstrom resolution. Four disulfide bridges in the extracellular domain, combined with a subtle repacking of the transmembrane helices relative to the adrenergic and rhodopsin receptor structures, define a pocket distinct from that of other structurally determined GPCRs. The arrangement allows for the binding of the antagonist in an extended conformation, perpendicular to the membrane plane. The binding site highlights an integral role for the extracellular loops, together with the helical core, in ligand recognition by this class of GPCRs and suggests a role for ZM241385 in restricting the movement of a tryptophan residue important in the activation mechanism of the class A receptors.


  • Organizational Affiliation

    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037 USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Human Adenosine A2A receptor/T4 lysozyme chimera488Homo sapiensTequatrovirus T4Mutation(s): 0 
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 
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP00720P29274
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZMA
Query on ZMA

Download Ideal Coordinates CCD File 
B [auth A]4-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenol
C16 H15 N7 O2
PWTBZOIUWZOPFT-UHFFFAOYSA-N
STE
Query on STE

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A]
STEARIC ACID
C18 H36 O2
QIQXTHQIDYTFRH-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
J [auth A]
K [auth A]
L [auth A]
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
ZMA BindingDB:  3EML Ki: min: 0.1, max: 64 (nM) from 16 assay(s)
Kd: 0.22 (nM) from 1 assay(s)
IC50: min: 0.68, max: 81 (nM) from 7 assay(s)
PDBBind:  3EML Kd: 1.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.198 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.736α = 90
b = 76.932β = 101.32
c = 86.553γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-10-14
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-08-08
    Changes: Other
  • Version 1.3: 2017-08-02
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description