5I9I

Crystal structure of LP_PLA2 in complex with Darapladib


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Structural and Thermodynamic Characterization of Protein-Ligand Interactions Formed between Lipoprotein-Associated Phospholipase A2 and Inhibitors

Liu, Q.F.Chen, X.D.Chen, W.Y.Yuan, X.J.Su, H.X.Shen, J.H.Xu, Y.C.

(2016) J Med Chem 59: 5115-5120

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b00282
  • Primary Citation of Related Structures:  
    5I8P, 5I9I

  • PubMed Abstract: 

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) represents a promising therapeutic target for atherosclerosis and Alzheimer's disease. Here we reported the first crystal structures of Lp-PLA2 bound with reversible inhibitors and the thermodynamic characterization of complexes. High rigidity of Lp-PLA2 structure and similar binding modes of inhibitors with completely different scaffolds are revealed. It not only provides the molecular basis for inhibitory activity but also sheds light on the essential features of Lp-PLA2 recognition with reversible inhibitors.


  • Organizational Affiliation

    School of Life Science and Technology, ShanghaiTech University , Shanghai 200031, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Platelet-activating factor acetylhydrolase
A, B
388Homo sapiensMutation(s): 0 
Gene Names: PLA2G7PAFAH
EC: 3.1.1.47
UniProt & NIH Common Fund Data Resources
Find proteins for Q13093 (Homo sapiens)
Explore Q13093 
Go to UniProtKB:  Q13093
PHAROS:  Q13093
GTEx:  ENSG00000146070 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13093
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5HV
Query on 5HV

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N-[2-(diethylamino)ethyl]-2-{2-[(4-fluorobenzyl)sulfanyl]-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl}-N-{[ 4'-(trifluoromethyl)biphenyl-4-yl]methyl}acetamide
C36 H38 F4 N4 O2 S
WDPFJWLDPVQCAJ-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth B],
F [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
5HV BindingDB:  5I9I Ki: 110 (nM) from 1 assay(s)
Kd: 5 (nM) from 1 assay(s)
IC50: min: 0.04, max: 49 (nM) from 11 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 115.9α = 90
b = 82.41β = 115.5
c = 96.47γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XSCALEdata scaling
PHASERmodel building
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-15
    Type: Initial release
  • Version 1.1: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary