5I8P

Crystal structure of LP_PLA2 in complex with novel inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.37 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 

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Ligand Structure Quality Assessment 


This is version 1.2 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: PLA2G7, PAFAH
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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
VQ7
Query on VQ7
Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]		6-[1,1-bis(oxidanylidene)-1,4-thiazinan-4-yl]-4-[[4-[4-chloranyl-3-(trifluoromethyl)phenoxy]-3,5-bis(fluoranyl)phenyl]methoxy]-1-methyl-pyrimidin-2-one
C23 H19 Cl F5 N3 O5 S
FLCSHCSBIFPQJJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
VQ7 Binding MOAD:  5I8P Kd: 64 (nM) from 1 assay(s)
BindingDB:  5I8P Kd: 1.9 (nM) from 1 assay(s)
IC50: 1.7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.37 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.208 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 115.82α = 90
b = 82.75β = 115.44
c = 96.39γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
PHASERmodel building
PHENIXrefinement
PDB_EXTRACTdata extraction

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-15
    Type: Initial release
  • Version 1.1: 2017-10-04
    Changes: Data collection, Derived calculations
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description