3AN4

Human PPAR gamma ligand binding domain in complex with a gamma selective agonist MO4R

PDB DOI: https://doi.org/10.2210/pdb3AN4/pdb

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

Deposited: 2010-08-30 Released: 2011-07-27
Deposition Author(s): Oyama, T., Ohashi, M., Waku, T., Miyachi, H., Morikawa, K.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.30 ?
R-Value Free:
0.288 (Depositor), 0.290 (DCC)
R-Value Work:
0.232 (Depositor), 0.220 (DCC)
R-Value Observed:
0.232 (Depositor)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Design, Synthesis, and Structural Analysis of Phenylpropanoic Acid-Type PPAR gamma-Selective Agonists: Discovery of Reversed Stereochemistry-Activity Relationship

Ohashi, M., Oyama, T., Nakagome, I., Satoh, M., Nishio, Y., Nobusada, H., Hirono, S., Morikawa, K., Hashimoto, Y., Miyachi, H.

(2011) J Med Chem 54: 331-341

PubMed: 21128600 Search on PubMed
DOI: https://doi.org/10.1021/jm101233f
Primary Citation of Related Structures:
3AN3, 3AN4

PubMed Abstract:
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and computational studies of α-benzylphenylpropanoic acid PPARγ agonists. Interestingly, these compounds show a reversal of the stereochemistry-transactivation activity relationship observed with other phenylpropanoic acid ligands.

Organizational Affiliation

Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.

Macromolecule Content

Total Structure Weight: 65.63 kDa
Atom Count: 4,273
Modelled Residue Count: 519
Deposited Residue Count: 572
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Peroxisome proliferator-activated receptor gamma	A, B	286	Homo sapiens	Mutation(s): 0 Gene Names: PPARG, NR1C3
UniProt & NIH Common Fund Data Resources
Find proteins for P37231 (Homo sapiens) Explore P37231 Go to UniProtKB: P37231
PHAROS: P37231 GTEx: ENSG00000132170
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P37231
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 1 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
M7R Query on M7R 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]	(2R)-2-benzyl-3-(4-propoxy-3-{[({4-[(3S,5S,7S)-tricyclo[3.3.1.1~3,7~]dec-1-yl]phenyl}carbonyl)amino]methyl}phenyl)propanoic acid C₃₇ H₄₃ N O₄ XYMQLACGAYNBRX-FJRQOFADSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
M7R	BindingDB: 3AN4	EC50: 3.6 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.30 ?
R-Value Free: 0.288 (Depositor), 0.290 (DCC)
R-Value Work: 0.232 (Depositor), 0.220 (DCC)
R-Value Observed: 0.232 (Depositor)

Space Group: C 1 2 1

Unit Cell:

Length ( ? )	Angle ( ? )
a = 93.391	α = 90
b = 61.271	β = 102.82
c = 118.871	γ = 90

Software Package:

Software Name	Purpose
HKL-2000	data collection
CNS	refinement
HKL-2000	data reduction
HKL-2000	data scaling
CNS	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2011-07-27

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2011-07-27
Type: Initial release
Version 1.1: 2023-11-01
Changes: Data collection, Database references, Derived calculations, Refinement description