4IAR

Crystal structure of the chimeric protein of 5-HT1B-BRIL in complex with ergotamine (PSI Community Target)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.7 of the entry. See complete history


Literature

Structural basis for molecular recognition at serotonin receptors.

Wang, C.Jiang, Y.Ma, J.Wu, H.Wacker, D.Katritch, V.Han, G.W.Liu, W.Huang, X.P.Vardy, E.McCorvy, J.D.Gao, X.Zhou, X.E.Melcher, K.Zhang, C.Bai, F.Yang, H.Yang, L.Jiang, H.Roth, B.L.Cherezov, V.Stevens, R.C.Xu, H.E.

(2013) Science 340: 610-614

  • DOI: https://doi.org/10.1126/science.1232807
  • Primary Citation of Related Structures:  
    4IAQ, 4IAR

  • PubMed Abstract: 

    Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Chimera protein of human 5-hydroxytryptamine receptor 1B and E. Coli soluble cytochrome b562401Homo sapiensEscherichia coliMutation(s): 4 
Gene Names: HTR1BHTR1DBcybC
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P28222 (Homo sapiens)
Explore P28222 
Go to UniProtKB:  P28222
PHAROS:  P28222
GTEx:  ENSG00000135312 
Find proteins for P0ABE7 (Escherichia coli)
Explore P0ABE7 
Go to UniProtKB:  P0ABE7
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP28222P0ABE7
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ERM
Query on ERM

Download Ideal Coordinates CCD File 
B [auth A]Ergotamine
C33 H35 N5 O5
XCGSFFUVFURLIX-VFGNJEKYSA-N
OLB
Query on OLB

Download Ideal Coordinates CCD File 
C [auth A](2S)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate
C21 H40 O4
RZRNAYUHWVFMIP-QJRAZLAKSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 195.29α = 90
b = 45.5β = 95.45
c = 74.28γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
BUSTERrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2013-03-13
    Type: Initial release
  • Version 1.1: 2013-04-10
    Changes: Database references
  • Version 1.2: 2013-05-15
    Changes: Database references
  • Version 1.3: 2013-12-18
    Changes: Derived calculations
  • Version 1.4: 2017-06-07
    Changes: Database references, Structure summary
  • Version 1.5: 2017-11-15
    Changes: Refinement description
  • Version 1.6: 2022-02-02
    Changes: Database references, Derived calculations
  • Version 1.7: 2023-09-20
    Changes: Data collection, Refinement description