3OTQ

Soluble Epoxide Hydrolase in complex with pyrazole antagonist

PDB DOI: https://doi.org/10.2210/pdb3OTQ/pdb

Classification: HYDROLASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2010-09-13 Released: 2010-10-27
Deposition Author(s): Farrow, N.A.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.318
R-Value Work: 0.230

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain.

Lo, H.Y., Man, C.C., Fleck, R.W., Farrow, N.A., Ingraham, R.H., Kukulka, A., Proudfoot, J.R., Betageri, R., Kirrane, T., Patel, U., Sharma, R., Hoermann, M.A., Kabcenell, A., Lombaert, S.D.

(2010) Bioorg Med Chem Lett 20: 6379-6383

PubMed: 20934334 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2010.09.095
Primary Citation of Related Structures:
3OTQ

PubMed Abstract:
A novel series of pyrazole sEH inhibitors is reported. Lead optimization efforts to replace the aniline core are also described. In particular, 2-pyridine, 3-pyridine and pyridazine analogs are potent sEH inhibitors with favorable CYP3A4 inhibitory and microsomal stability profiles.

Organizational Affiliation

Boehringer Ingelheim Pharmaceuticals Inc., Biomolecular Screening, 900 Ridgebury Rd., PO Box 368, Ridgefield, CT 06877, USA. [email protected]

Macromolecule Content

Total Structure Weight: 63.06 kDa
Atom Count: 4,385
Modelled Residue Count: 545
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
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 (UniProt)
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 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
MZL Query on MZL 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]	N-[4-(5-ethyl-3-pyridin-3-yl-1H-pyrazol-1-yl)phenyl]pyridine-3-carboxamide C₂₂ H₁₉ N₅ O CCAFHMPMIJBDRP-UHFFFAOYSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
MZL	BindingDB: 3OTQ	IC50: 41 (nM) from 1 assay(s)
MZL	PDBBind: 3OTQ	IC50: 41 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 3.00 Å
R-Value Free: 0.318
R-Value Work: 0.230
Space Group: P 6₅ 2 2

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 92.993	α = 90
b = 92.993	β = 90
c = 243.651	γ = 120

Software Package:

Software Name	Purpose
CrystalClear	data collection
CNX	refinement

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-10-27

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2010-10-27
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2021-02-24
Changes: Derived calculations
Version 1.3: 2024-02-21
Changes: Data collection, Database references

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.