4Z35

Crystal Structure of Human Lysophosphatidic Acid Receptor 1 in complex with ONO-9910539


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.265 
  • R-Value Observed: 0.266 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal Structure of Antagonist Bound Human Lysophosphatidic Acid Receptor 1.

Chrencik, J.E.Roth, C.B.Terakado, M.Kurata, H.Omi, R.Kihara, Y.Warshaviak, D.Nakade, S.Asmar-Rovira, G.Mileni, M.Mizuno, H.Griffith, M.T.Rodgers, C.Han, G.W.Velasquez, J.Chun, J.Stevens, R.C.Hanson, M.A.

(2015) Cell 161: 1633-1643

  • DOI: https://doi.org/10.1016/j.cell.2015.06.002
  • Primary Citation of Related Structures:  
    4Z34, 4Z35, 4Z36

  • PubMed Abstract: 

    Lipid biology continues to emerge as an area of significant therapeutic interest, particularly as the result of an enhanced understanding of the wealth of signaling molecules with diverse physiological properties. This growth in knowledge is epitomized by lysophosphatidic acid (LPA), which functions through interactions with at least six cognate G protein-coupled receptors. Herein, we present three crystal structures of LPA1 in complex with antagonist tool compounds selected and designed through structural and stability analyses. Structural analysis combined with molecular dynamics identified a basis for ligand access to the LPA1 binding pocket from the extracellular space contrasting with the proposed access for the sphingosine 1-phosphate receptor. Characteristics of the LPA1 binding pocket raise the possibility of promiscuous ligand recognition of phosphorylated endocannabinoids. Cell-based assays confirmed this hypothesis, linking the distinct receptor systems through metabolically related ligands with potential functional and therapeutic implications for treatment of disease.


  • Organizational Affiliation

    Department of Structural Discovery, Receptos, San Diego, CA 92121, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lysophosphatidic acid receptor 1,Soluble cytochrome b562464Homo sapiensEscherichia coliMutation(s): 2 
Gene Names: LPAR1EDG2LPA1cybC
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P0ABE7 (Escherichia coli)
Explore P0ABE7 
Go to UniProtKB:  P0ABE7
Find proteins for Q92633 (Homo sapiens)
Explore Q92633 
Go to UniProtKB:  Q92633
PHAROS:  Q92633
GTEx:  ENSG00000198121 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsP0ABE7Q92633
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ON9
Query on ON9

Download Ideal Coordinates CCD File 
B [auth A]3-{1-[(2S,3S)-3-(4-acetyl-3,5-dimethoxyphenyl)-2-(2,3-dihydro-1H-inden-2-ylmethyl)-3-hydroxypropyl]-4-(methoxycarbonyl)-1H-pyrrol-3-yl}propanoic acid
C32 H37 N O8
URHZQBASTULQKJ-VVFBEHOQSA-N
1WV
Query on 1WV

Download Ideal Coordinates CCD File 
C [auth A](2S)-2,3-dihydroxypropyl (7Z)-tetradec-7-enoate
C17 H32 O4
LVBAGTJIDOCNIJ-INIZCTEOSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.265 
  • R-Value Observed: 0.266 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 34.61α = 90
b = 112.4β = 90
c = 155.67γ = 90
Software Package:
Software NamePurpose
BUSTERrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2015-06-03
    Type: Initial release
  • Version 1.1: 2015-07-01
    Changes: Database references
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description, Source and taxonomy, Structure summary