3NY9

Crystal structure of the human beta2 adrenergic receptor in complex with a novel inverse agonist


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.84 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.222 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Conserved Binding Mode of Human beta(2) Adrenergic Receptor Inverse Agonists and Antagonist Revealed by X-ray Crystallography

Wacker, D.Fenalti, G.Brown, M.A.Katritch, V.Abagyan, R.Cherezov, V.Stevens, R.C.

(2010) J Am Chem Soc 132: 11443-11445

  • DOI: https://doi.org/10.1021/ja105108q
  • Primary Citation of Related Structures:  
    3NY8, 3NY9, 3NYA

  • PubMed Abstract: 

    G protein-coupled receptors (GPCRs) represent a large fraction of current pharmaceutical targets, and of the GPCRs, the beta(2) adrenergic receptor (beta(2)AR) is one of the most extensively studied. Previously, the X-ray crystal structure of beta(2)AR has been determined in complex with two partial inverse agonists, but the global impact of additional ligands on the structure or local impacts on the binding site are not well-understood. To assess the extent of such ligand-induced conformational differences, we determined the crystal structures of a previously described engineered beta(2)AR construct in complex with two inverse agonists: ICI 118,551 (2.8 A), a recently described compound (2.8 A) (Kolb et al, 2009), and the antagonist alprenolol (3.1 A). The structures show the same overall fold observed for the previous beta(2)AR structures and demonstrate that the ligand binding site can accommodate compounds of different chemical and pharmacological properties with only minor local structural rearrangements. All three compounds contain a hydroxy-amine motif that establishes a conserved hydrogen bond network with the receptor and chemically diverse aromatic moieties that form distinct interactions with beta(2)AR. Furthermore, receptor ligand cross-docking experiments revealed that a single beta(2)AR complex can be suitable for docking of a range of antagonists and inverse agonists but also indicate that additional ligand-receptor structures may be useful to further improve performance for in-silico docking or lead-optimization in drug design.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2 adrenergic receptor, Lysozyme490Homo sapiensTequatrovirus T4Mutation(s): 6 
Gene Names: ADRB2ADRB2RB2ARE
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P07550 (Homo sapiens)
Explore P07550 
Go to UniProtKB:  P07550
PHAROS:  P07550
GTEx:  ENSG00000169252 
Find proteins for P00720 (Enterobacteria phage T4)
Explore P00720 
Go to UniProtKB:  P00720
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP00720P07550
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CLR
Query on CLR

Download Ideal Coordinates CCD File 
B [auth A],
C [auth A]
CHOLESTEROL
C27 H46 O
HVYWMOMLDIMFJA-DPAQBDIFSA-N
OLC
Query on OLC

Download Ideal Coordinates CCD File 
E [auth A](2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
C21 H40 O4
RZRNAYUHWVFMIP-GDCKJWNLSA-N
JSZ
Query on JSZ

Download Ideal Coordinates CCD File 
D [auth A]ethyl 4-({(2S)-2-hydroxy-3-[(1-methylethyl)amino]propyl}oxy)-3-methyl-1-benzofuran-2-carboxylate
C18 H25 N O5
QVJVMNUTCGTBCH-ZDUSSCGKSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.84 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.222 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.58α = 90
b = 75.9β = 90
c = 174.18γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
XDSdata reduction
XSCALEdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2010-08-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-05-23
    Changes: Database references
  • Version 1.3: 2012-08-08
    Changes: Other
  • Version 1.4: 2017-08-02
    Changes: Refinement description, Source and taxonomy
  • Version 1.5: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description