7BVQ

Structure of human beta1 adrenergic receptor bound to carazolol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Binding pathway determines norepinephrine selectivity for the human beta 1 AR over beta 2 AR.

Xu, X.Kaindl, J.Clark, M.J.Hubner, H.Hirata, K.Sunahara, R.K.Gmeiner, P.Kobilka, B.K.Liu, X.

(2021) Cell Res 31: 569-579

  • DOI: https://doi.org/10.1038/s41422-020-00424-2
  • Primary Citation of Related Structures:  
    7BTS, 7BU6, 7BU7, 7BVQ

  • PubMed Abstract: 

    Beta adrenergic receptors (βARs) mediate physiologic responses to the catecholamines epinephrine and norepinephrine released by the sympathetic nervous system. While the hormone epinephrine binds β 1 AR and β 2 AR with similar affinity, the smaller neurotransmitter norepinephrine is approximately tenfold selective for the β 1 AR. To understand the structural basis for this physiologically important selectivity, we solved the crystal structures of the human β 1 AR bound to an antagonist carazolol and different agonists including norepinephrine, epinephrine and BI-167107. Structural comparison revealed that the catecholamine-binding pockets are identical between β 1 AR and β 2 AR, but the extracellular vestibules have different shapes and electrostatic properties. Metadynamics simulations and mutagenesis studies revealed that these differences influence the path norepinephrine takes to the orthosteric pocket and contribute to the different association rates and thus different affinities.


  • Organizational Affiliation

    Department of Pharmacology, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endolysin,Beta-1 adrenergic receptor chimera
A, B
462Tequatrovirus T4Homo sapiens
This entity is chimeric
Mutation(s): 2 
Gene Names: eT4Tp126
EC: 3.2.1.17
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for D9IEF7 (Enterobacteria phage T4)
Explore D9IEF7 
Go to UniProtKB:  D9IEF7
Find proteins for P08588 (Homo sapiens)
Explore P08588 
Go to UniProtKB:  P08588
PHAROS:  P08588
GTEx:  ENSG00000043591 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsD9IEF7P08588
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose
C
2N/A
Glycosylation Resources
GlyTouCan:  G07411ON
GlyCosmos:  G07411ON
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CLR
Query on CLR

Download Ideal Coordinates CCD File 
D [auth A]CHOLESTEROL
C27 H46 O
HVYWMOMLDIMFJA-DPAQBDIFSA-N
1WV
Query on 1WV

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L [auth A],
V [auth B]
(2S)-2,3-dihydroxypropyl (7Z)-tetradec-7-enoate
C17 H32 O4
LVBAGTJIDOCNIJ-INIZCTEOSA-N
CAU (Subject of Investigation/LOI)
Query on CAU

Download Ideal Coordinates CCD File 
E [auth A],
S [auth B]
(2S)-1-(9H-Carbazol-4-yloxy)-3-(isopropylamino)propan-2-ol
C18 H22 N2 O2
BQXQGZPYHWWCEB-ZDUSSCGKSA-N
PG4
Query on PG4

Download Ideal Coordinates CCD File 
P [auth A],
Q [auth A],
R [auth A],
W [auth B]
TETRAETHYLENE GLYCOL
C8 H18 O5
UWHCKJMYHZGTIT-UHFFFAOYSA-N
CIT
Query on CIT

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N [auth A],
O [auth A]
CITRIC ACID
C6 H8 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-N
SO4
Query on SO4

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F [auth A]
G [auth A]
H [auth A]
I [auth A]
J [auth A]
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
T [auth B],
U [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
NA
Query on NA

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M [auth A]SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.227 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.134α = 92.137
b = 52.825β = 90.714
c = 142.749γ = 116.647
Software Package:
Software NamePurpose
PHENIXrefinement
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-12-02
    Type: Initial release
  • Version 1.1: 2021-05-12
    Changes: Database references
  • Version 1.2: 2023-11-29
    Changes: Data collection, Database references, Refinement description