3H0A

Crystal Structure of Peroxisome Proliferator-Activated Receptor Gamma (PPARg) and Retinoic Acid Receptor Alpha (RXRa) in Complex with 9-cis Retinoic Acid, Co-activator Peptide, and a Partial Agonist

PDB DOI: https://doi.org/10.2210/pdb3H0A/pdb

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

Deposited: 2009-04-08 Released: 2009-06-09
Deposition Author(s): Wang, Z., Sudom, A., Walker, N.P.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.342
R-Value Work: 0.246
R-Value Observed: 0.251

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Identification of a PPARdelta agonist with partial agonistic activity on PPARgamma.

Connors, R.V., Wang, Z., Harrison, M., Zhang, A., Wanska, M., Hiscock, S., Fox, B., Dore, M., Labelle, M., Sudom, A., Johnstone, S., Liu, J., Walker, N.P., Chai, A., Siegler, K., Li, Y., Coward, P.

(2009) Bioorg Med Chem Lett 19: 3550-3554

PubMed: 19464171 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2009.04.151
Primary Citation of Related Structures:
3GZ9, 3H0A

PubMed Abstract:
The discovery and optimization of a series of potent PPARdelta full agonists with partial agonistic activity against PPARgamma is described.

Organizational Affiliation

Department of Chemistry, Amgen, 1120 Veterans Blvd., South San Francisco, CA 94080, USA. [email protected]

Macromolecule Content

Total Structure Weight: 60.3 kDa
Atom Count: 4,147
Modelled Residue Count: 498
Deposited Residue Count: 524
Unique protein chains: 3

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Retinoic acid receptor RXR-alpha	A	228	Homo sapiens	Mutation(s): 0 Gene Names: RXRA, NR2B1
UniProt & NIH Common Fund Data Resources
Find proteins for P19793 (Homo sapiens) Explore P19793 Go to UniProtKB: P19793
PHAROS: P19793 GTEx: ENSG00000186350
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P19793
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Peroxisome proliferator-activated receptor gamma	B [auth D]	272	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

Find similar proteins by: Sequence | 3D Structure

Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Nuclear receptor coactivator 1, Co-activator Peptide	C [auth B], D [auth E]	12	Homo sapiens	Mutation(s): 0 EC: 2.3.1.48
UniProt & NIH Common Fund Data Resources
Find proteins for Q15788 (Homo sapiens) Explore Q15788 Go to UniProtKB: Q15788
PHAROS: Q15788 GTEx: ENSG00000084676
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q15788
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
D30 Query on D30 Download Ideal Coordinates CCD File SDF format, chain F [auth D] MOL2 format, chain F [auth D] mmCIF format, chain F [auth D]	F [auth D]	[(4-{[2-(pent-2-yn-1-yloxy)-4-{[4-(trifluoromethyl)phenoxy]methyl}phenyl]sulfanyl}-5,6,7,8-tetrahydronaphthalen-1-yl)oxy]acetic acid C₃₁ H₂₉ F₃ O₅ S SIHDSSYICQEWRS-UHFFFAOYSA-N		Interactions Focus chain F [auth D] Interactions & Density Focus chain F [auth D]
9RA Query on 9RA Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethenyl]benzoic acid C₂₄ H₂₈ O₂ NAVMQTYZDKMPEU-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]

Binding Affinity Annotations
ID	Source	Binding Affinity
9RA	BindingDB: 3H0A	Ki: min: 5.9, max: 379 (nM) from 14 assay(s)
		Kd: min: 7, max: 1890 (nM) from 13 assay(s)
		IC50: 632 (nM) from 1 assay(s)
		EC50: min: 2.7, max: 149 (nM) from 21 assay(s)
D30	PDBBind: 3H0A	Ki: 33 (nM) from 1 assay(s)
	BindingDB: 3H0A	Ki: 33 (nM) from 1 assay(s)
	BindingDB: 3H0A	EC50: 160 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.10 Å
R-Value Free: 0.342
R-Value Work: 0.246
R-Value Observed: 0.251
Space Group: C 1 2 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 179.258	α = 90
b = 53.825	β = 107.74
c = 67.108	γ = 90

Software Package:

Software Name	Purpose
MOSFLM	data reduction
SCALA	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
ADSC	data collection

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2009-06-09

Deposition Author(s):

Wang, Z.

Sudom, A.

Walker, N.P.

Revision History (Full details and data files)

Version 1.0: 2009-06-09
Type: Initial release
Version 1.1: 2011-07-13
Changes: Version format compliance
Version 1.2: 2014-04-02
Changes: Source and taxonomy
Version 1.3: 2024-02-21
Changes: Data collection, Database references, Derived calculations