4YAY

XFEL structure of human Angiotensin Receptor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.8 of the entry. See complete history


Literature

Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.

Zhang, H.Unal, H.Gati, C.Han, G.W.Liu, W.Zatsepin, N.A.James, D.Wang, D.Nelson, G.Weierstall, U.Sawaya, M.R.Xu, Q.Messerschmidt, M.Williams, G.J.Boutet, S.Yefanov, O.M.White, T.A.Wang, C.Ishchenko, A.Tirupula, K.C.Desnoyer, R.Coe, J.Conrad, C.E.Fromme, P.Stevens, R.C.Katritch, V.Karnik, S.S.Cherezov, V.

(2015) Cell 161: 833-844

  • DOI: https://doi.org/10.1016/j.cell.2015.04.011
  • Primary Citation of Related Structures:  
    4YAY

  • PubMed Abstract: 

    Angiotensin II type 1 receptor (AT(1)R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT(1)R blockers (ARBs), the structural basis for AT(1)R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high-quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT(1)R in complex with its selective antagonist ZD7155 at 2.9-Å resolution. The AT(1)R-ZD7155 complex structure revealed key structural features of AT(1)R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT(1)R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT(1)R structure-function relationship and structure-based drug design.


  • Organizational Affiliation

    Department of Biological Sciences, Bridge Institute, 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
Soluble cytochrome b562,Type-1 angiotensin II receptor414Escherichia coliHomo sapiens
This entity is chimeric
Mutation(s): 3 
Gene Names: cybCAGTR1AGTR1AAGTR1BAT2R1AT2R1B
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P30556 (Homo sapiens)
Explore P30556 
Go to UniProtKB:  P30556
PHAROS:  P30556
GTEx:  ENSG00000144891 
Find proteins for P0ABE7 (Escherichia coli)
Explore P0ABE7 
Go to UniProtKB:  P0ABE7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP0ABE7P30556
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZD7
Query on ZD7

Download Ideal Coordinates CCD File 
B [auth A]5,7-diethyl-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-3,4-dihydro-1,6-naphthyridin-2(1H)-one
C26 H26 N6 O
BFVNEYDCFJNLGN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ZD7 BindingDB:  4YAY IC50: 3.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.8α = 90
b = 41β = 99.4
c = 167.7γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
PHASERphasing
CrystFELdata scaling
CrystFELdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesU54 GM094618

Revision History  (Full details and data files)

  • Version 1.0: 2015-04-22
    Type: Initial release
  • Version 1.1: 2015-05-06
    Changes: Structure summary
  • Version 1.2: 2015-05-13
    Changes: Database references
  • Version 1.3: 2015-05-27
    Changes: Database references
  • Version 1.4: 2017-09-06
    Changes: Author supporting evidence, Derived calculations, Source and taxonomy
  • Version 1.5: 2017-11-22
    Changes: Refinement description
  • Version 1.6: 2018-02-14
    Changes: Data collection
  • Version 1.7: 2019-12-25
    Changes: Author supporting evidence
  • Version 1.8: 2023-08-16
    Changes: Data collection, Database references