4EIY

Crystal structure of the chimeric protein of A2aAR-BRIL in complex with ZM241385 at 1.8A resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural basis for allosteric regulation of GPCRs by sodium ions.

Liu, W.Chun, E.Thompson, A.A.Chubukov, P.Xu, F.Katritch, V.Han, G.W.Roth, C.B.Heitman, L.H.IJzerman, A.P.Cherezov, V.Stevens, R.C.

(2012) Science 337: 232-236

  • DOI: https://doi.org/10.1126/science.1219218
  • Primary Citation of Related Structures:  
    4EIY

  • PubMed Abstract: 

    Pharmacological responses of G protein-coupled receptors (GPCRs) can be fine-tuned by allosteric modulators. Structural studies of such effects have been limited due to the medium resolution of GPCR structures. We reengineered the human A(2A) adenosine receptor by replacing its third intracellular loop with apocytochrome b(562)RIL and solved the structure at 1.8 angstrom resolution. The high-resolution structure allowed us to identify 57 ordered water molecules inside the receptor comprising three major clusters. The central cluster harbors a putative sodium ion bound to the highly conserved aspartate residue Asp(2.50). Additionally, two cholesterols stabilize the conformation of helix VI, and one of 23 ordered lipids intercalates inside the ligand-binding pocket. These high-resolution details shed light on the potential role of structured water molecules, sodium ions, and lipids/cholesterol in GPCR stabilization and function.


  • Organizational Affiliation

    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Adenosine receptor A2a/Soluble cytochrome b562 chimera447Homo sapiensEscherichia coliMutation(s): 3 
Gene Names: AA2AR_HUMANADORA2ADORA2AcybC
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P0ABE7 (Escherichia coli)
Explore P0ABE7 
Go to UniProtKB:  P0ABE7
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 GroupsP0ABE7P29274
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CLR
Query on CLR

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
F [auth A]
CHOLESTEROL
C27 H46 O
HVYWMOMLDIMFJA-DPAQBDIFSA-N
OLB
Query on OLB

Download Ideal Coordinates CCD File 
AA [auth A](2S)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
C21 H40 O4
RZRNAYUHWVFMIP-QJRAZLAKSA-N
OLC
Query on OLC

Download Ideal Coordinates CCD File 
BA [auth A]
CA [auth A]
W [auth A]
X [auth A]
Y [auth A]
BA [auth A],
CA [auth A],
W [auth A],
X [auth A],
Y [auth A],
Z [auth A]
(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
C21 H40 O4
RZRNAYUHWVFMIP-GDCKJWNLSA-N
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
OLA
Query on OLA

Download Ideal Coordinates CCD File 
G [auth A]
H [auth A]
I [auth A]
J [auth A]
K [auth A]
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
U [auth A],
V [auth A]
OLEIC ACID
C18 H34 O2
ZQPPMHVWECSIRJ-KTKRTIGZSA-N
PEG
Query on PEG

Download Ideal Coordinates CCD File 
DA [auth A],
EA [auth A]
DI(HYDROXYETHYL)ETHER
C4 H10 O3
MTHSVFCYNBDYFN-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
C [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ZMA BindingDB:  4EIY 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)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.213 
  • R-Value Work: 0.174 
  • R-Value Observed: 0.176 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.442α = 90
b = 179.516β = 90
c = 140.307γ = 90
Software Package:
Software NamePurpose
PHASERphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-25
    Type: Initial release
  • Version 1.1: 2012-08-01
    Changes: Database references
  • Version 1.2: 2017-08-16
    Changes: Data collection, Refinement description, Source and taxonomy
  • Version 1.3: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description