4HAI

Crystal structure of human soluble epoxide hydrolase complexed with N-cycloheptyl-1-(mesitylsulfonyl)piperidine-4-carboxamide.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Synthesis and structure-activity relationship of piperidine-derived non-urea soluble epoxide hydrolase inhibitors.

Pecic, S.Pakhomova, S.Newcomer, M.E.Morisseau, C.Hammock, B.D.Zhu, Z.Rinderspacher, A.Deng, S.X.

(2013) Bioorg Med Chem Lett 23: 417-421

  • DOI: https://doi.org/10.1016/j.bmcl.2012.11.084
  • Primary Citation of Related Structures:  
    4HAI

  • PubMed Abstract: 

    A series of potent amide non-urea inhibitors of soluble epoxide hydrolase (sEH) is disclosed. The inhibition of soluble epoxide hydrolase leads to elevated levels of epoxyeicosatrienoic acids (EETs), and thus inhibitors of sEH represent one of a novel approach to the development of vasodilatory and anti-inflammatory drugs. Structure-activities studies guided optimization of a lead compound, identified through high-throughput screening, gave rise to sub-nanomolar inhibitors of human sEH with stability in human liver microsomal assay suitable for preclinical development.


  • Organizational Affiliation

    Department of Medicine, Columbia University, 650 W 168th Street, BB1029, New York, NY 10032, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bifunctional epoxide hydrolase 2555Homo sapiensMutation(s): 0 
Gene Names: EPHX2
EC: 3.3.2.10 (PDB Primary Data), 3.1.3.76 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P34913 (Homo sapiens)
Explore P34913 
Go to UniProtKB:  P34913
PHAROS:  P34913
GTEx:  ENSG00000120915 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP34913
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
I23
Query on I23

Download Ideal Coordinates CCD File 
D [auth A]N-cycloheptyl-1-[(2,4,6-trimethylphenyl)sulfonyl]piperidine-4-carboxamide
C22 H34 N2 O3 S
GTZJATJFRQCZIY-UHFFFAOYSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
B [auth A]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
MG
Query on MG

Download Ideal Coordinates CCD File 
C [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
I23 PDBBind:  4HAI IC50: 7.9 (nM) from 1 assay(s)
BindingDB:  4HAI IC50: 7.9 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.55 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.183 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.32α = 90
b = 92.32β = 90
c = 243.982γ = 120
Software Package:
Software NamePurpose
xia2data scaling
MOLREPphasing
REFMACrefinement
xia2data reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-12-26
    Type: Initial release
  • Version 1.1: 2013-01-16
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description