5UNG

XFEL structure of human angiotensin II type 2 receptor (Orthorhombic form) in complex with compound 1 (N-benzyl-N-(2-ethyl-4-oxo-3-{[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl] methyl}-3,4-dihydroquinazolin-6-yl)thiophene-2-carboxamide)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.241 
  • R-Value Observed: 0.242 

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 selectivity and diversity in angiotensin II receptors.

Zhang, H.Han, G.W.Batyuk, A.Ishchenko, A.White, K.L.Patel, N.Sadybekov, A.Zamlynny, B.Rudd, M.T.Hollenstein, K.Tolstikova, A.White, T.A.Hunter, M.S.Weierstall, U.Liu, W.Babaoglu, K.Moore, E.L.Katz, R.D.Shipman, J.M.Garcia-Calvo, M.Sharma, S.Sheth, P.Soisson, S.M.Stevens, R.C.Katritch, V.Cherezov, V.

(2017) Nature 544: 327-332

  • DOI: https://doi.org/10.1038/nature22035
  • Primary Citation of Related Structures:  
    5UNF, 5UNG, 5UNH

  • PubMed Abstract: 

    The angiotensin II receptors AT 1 R and AT 2 R serve as key components of the renin-angiotensin-aldosterone system. AT 1 R has a central role in the regulation of blood pressure, but the function of AT 2 R is unclear and it has a variety of reported effects. To identify the mechanisms that underlie the differences in function and ligand selectivity between these receptors, here we report crystal structures of human AT 2 R bound to an AT 2 R-selective ligand and to an AT 1 R/AT 2 R dual ligand, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G proteins or β-arrestins, in agreement with the lack of signalling responses in standard cellular assays. Structure-activity relationship, docking and mutagenesis studies revealed the crucial interactions for ligand binding and selectivity. Our results thus provide insights into the structural basis of the distinct functions of the angiotensin receptors, and may guide the design of new selective ligands.


  • Organizational Affiliation

    Department of Chemistry, Bridge Institute, University of Southern California, Los Angeles, California 90089, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chimera protein of Type-2 angiotensin II receptor and Soluble cytochrome b562A [auth B]411Escherichia coliHomo sapiens
This entity is chimeric
Mutation(s): 3 
Gene Names: cybCAGTR2
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P0ABE7 (Escherichia coli)
Explore P0ABE7 
Go to UniProtKB:  P0ABE7
Find proteins for P50052 (Homo sapiens)
Explore P50052 
Go to UniProtKB:  P50052
PHAROS:  P50052
GTEx:  ENSG00000180772 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP0ABE7P50052
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
8ES
Query on 8ES

Download Ideal Coordinates CCD File 
B
N-benzyl-N-(2-ethyl-4-oxo-3-{[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl}-3,4-dihydroquinazolin-6-yl)thiophene-2-carboxamide
C36 H29 N7 O2 S
KDPHUUTUDFDLBT-UHFFFAOYSA-N
OLC
Query on OLC

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

Download Ideal Coordinates CCD File 
D [auth B]OLEIC ACID
C18 H34 O2
ZQPPMHVWECSIRJ-KTKRTIGZSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.262 
  • R-Value Work: 0.241 
  • R-Value Observed: 0.242 
  • Space Group: P 21 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.26α = 90
b = 78.79β = 90
c = 93.41γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
CrystFELdata reduction
CrystFELdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2017-04-05
    Type: Initial release
  • Version 1.1: 2017-05-10
    Changes: Data collection, Database references
  • Version 1.2: 2018-11-28
    Changes: Data collection
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Refinement description