6PS4

XFEL beta2 AR structure by ligand exchange from Timolol to ICI-118551.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report

Currently 6PS4 does not have a validation slider image.


This is version 1.3 of the entry. See complete history


Literature

Toward G protein-coupled receptor structure-based drug design using X-ray lasers.

Ishchenko, A.Stauch, B.Han, G.W.Batyuk, A.Shiriaeva, A.Li, C.Zatsepin, N.Weierstall, U.Liu, W.Nango, E.Nakane, T.Tanaka, R.Tono, K.Joti, Y.Iwata, S.Moraes, I.Gati, C.Cherezov, V.

(2019) IUCrJ 6: 1106-1119

  • DOI: https://doi.org/10.1107/S2052252519013137
  • Primary Citation of Related Structures:  
    6PRZ, 6PS0, 6PS1, 6PS2, 6PS3, 6PS4, 6PS5, 6PS6, 6PS7, 6PS8

  • PubMed Abstract: 

    Rational structure-based drug design (SBDD) relies on the availability of a large number of co-crystal structures to map the ligand-binding pocket of the target protein and use this information for lead-compound optimization via an iterative process. While SBDD has proven successful for many drug-discovery projects, its application to G protein-coupled receptors (GPCRs) has been limited owing to extreme difficulties with their crystallization. Here, a method is presented for the rapid determination of multiple co-crystal structures for a target GPCR in complex with various ligands, taking advantage of the serial femtosecond crystallography approach, which obviates the need for large crystals and requires only submilligram quantities of purified protein. The method was applied to the human β 2 -adrenergic receptor, resulting in eight room-temperature co-crystal structures with six different ligands, including previously unreported structures with carvedilol and propranolol. The generality of the proposed method was tested with three other receptors. This approach has the potential to enable SBDD for GPCRs and other difficult-to-crystallize membrane proteins.


  • Organizational Affiliation

    Bridge Institute, Departments of Chemistry and Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fusion protein of Beta-2 adrenergic receptor and T4 Lysozyme506Homo sapiensTequatrovirus T4Mutation(s): 6 
Gene Names: ADRB2ADRB2RB2AReT4Tp126
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 D9IEF7 (Enterobacteria phage T4)
Explore D9IEF7 
Go to UniProtKB:  D9IEF7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsD9IEF7P07550
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CLR
Query on CLR

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

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

Download Ideal Coordinates CCD File 
G [auth A],
H [auth A],
I [auth A],
J [auth A]
OLEIC ACID
C18 H34 O2
ZQPPMHVWECSIRJ-KTKRTIGZSA-N
JRZ (Subject of Investigation/LOI)
Query on JRZ

Download Ideal Coordinates CCD File 
B [auth A](2S,3S)-1-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]butan-2-ol
C17 H27 N O2
VFIDUCMKNJIJTO-XJKSGUPXSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth A],
D [auth A],
E [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.5α = 90
b = 76.2β = 90
c = 171.62γ = 90
Software Package:
Software NamePurpose
PHASERphasing
BUSTERrefinement
PDB_EXTRACTdata extraction
CrystFELdata reduction
CrystFELdata scaling

Structure Validation

View Full Validation Report

Currently 6PS4 does not have a validation slider image.



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesR35 GM127086

Revision History  (Full details and data files)

  • Version 1.0: 2019-11-13
    Type: Initial release
  • Version 1.1: 2019-12-25
    Changes: Database references
  • Version 1.2: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.3: 2023-10-11
    Changes: Data collection, Database references, Refinement description