4HAI

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

PDB DOI: https://doi.org/10.2210/pdb4HAI/pdb

Classification: hydrolase/hydrolase inhibitor
Organism(s): Homo sapiens
Expression System: Spodoptera frugiperda
Mutation(s): No

Deposited: 2012-09-26 Released: 2012-12-26
Deposition Author(s): Pecic, S., Pakhomova, S., Newcomer, M.E., Morisseau, C., Hammock, B.D., Zhu, Z., Deng, S.

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

Starting Model: experimental
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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

PubMed: 23237835 Search on PubMedSearch on PubMed Central
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.

Macromolecule Content

Total Structure Weight: 63.21 kDa
Atom Count: 4,389
Modelled Residue Count: 548
Deposited Residue Count: 555
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Bifunctional epoxide hydrolase 2	A	555	Homo sapiens	Mutation(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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P34913
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
I23 Query on I23 Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A] mmCIF format, chain D [auth A]	D [auth A]	N-cycloheptyl-1-[(2,4,6-trimethylphenyl)sulfonyl]piperidine-4-carboxamide C₂₂ H₃₄ N₂ O₃ S GTZJATJFRQCZIY-UHFFFAOYSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
PO4 Query on PO4 Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	PHOSPHATE ION O₄ P NBIIXXVUZAFLBC-UHFFFAOYSA-K		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
MG Query on MG Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	MAGNESIUM ION Mg JLVVSXFLKOJNIY-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
I23	PDBBind: 4HAI	IC50: 7.9 (nM) from 1 assay(s)
I23	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 = 92.32	α = 90
b = 92.32	β = 90
c = 243.982	γ = 120

Software Package:

Software Name	Purpose
xia2	data scaling
MOLREP	phasing
REFMAC	refinement
xia2	data reduction
SCALA	data scaling

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2012-12-26

Deposition Author(s):

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