5ZQU

Crystal structure of tetrameric RXRalpha-LBD complexed with partial agonist CBt-PMN

PDB DOI: https://doi.org/10.2210/pdb5ZQU/pdb

Classification: TRANSCRIPTION
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2018-04-20 Released: 2019-02-27
Deposition Author(s): Miyashita, Y., Numoto, N., Arulmozhiraja, S., Nakano, S., Matsuo, N., Shimizu, K., Kakuta, H., Ito, S., Ikura, T., Ito, N., Tokiwa, H.
Funding Organization(s): Japan Agency for Medical Research and Development (AMED)

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.270
R-Value Work: 0.222
R-Value Observed: 0.224

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

Dual conformation of the ligand induces the partial agonistic activity of retinoid X receptor alpha (RXR alpha ).

Miyashita, Y., Numoto, N., Arulmozhiraja, S., Nakano, S., Matsuo, N., Shimizu, K., Shibahara, O., Fujihara, M., Kakuta, H., Ito, S., Ikura, T., Ito, N., Tokiwa, H.

(2019) FEBS Lett 593: 242-250

PubMed: 30565665 Search on PubMed
DOI: https://doi.org/10.1002/1873-3468.13301
Primary Citation of Related Structures:
5ZQU

PubMed Abstract:
1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (CBt-PMN), a partial agonist of retinoid X receptor (RXR), has attracted attention due to its potential to treat type 2 diabetes and central nervous system diseases with reduced adverse effects of existing full agonists. Herein, we report the crystal structure of CBt-PMN-bound ligand-binding domain of human RXRα (hRXRα) and its biochemical characterization. Interestingly, the structure is a tetramer in nature, in which CBt-PMNs are clearly found binding in two different conformations. The dynamics of the hRXRα/CBt-PMN complex examined using molecular dynamics simulations suggest that the flexibility of the AF-2 interface depends on the conformation of the ligand. These facts reveal that the dual conformation of CBt-PMN in the complex is probably the reason behind its partial agonistic activity.

Organizational Affiliation

Department of Chemistry, Rikkyo University, Tokyo, Japan.

Macromolecule Content

Total Structure Weight: 111.56 kDa
Atom Count: 6,524
Modelled Residue Count: 789
Deposited Residue Count: 972
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Retinoic acid receptor RXR-alpha	A, B, C, D	243	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

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
9HF (Subject of Investigation/LOI) Query on 9HF Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain K [auth B] SDF format, chain O [auth C] SDF format, chain R [auth D] SDF format, chain S [auth D] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain K [auth B] MOL2 format, chain O [auth C] MOL2 format, chain R [auth D] MOL2 format, chain S [auth D] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain K [auth B] mmCIF format, chain O [auth C] mmCIF format, chain R [auth D] mmCIF format, chain S [auth D]	E [auth A] F [auth A] K [auth B] O [auth C] R [auth D] E [auth A], F [auth A], K [auth B], O [auth C], R [auth D], S [auth D]	1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl)benzotriazole-5-carboxylic acid C₂₂ H₂₅ N₃ O₂ QSRQAKVNYDAVIT-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain K [auth B] Focus chain O [auth C] Focus chain R [auth D] Focus chain S [auth D] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain K [auth B] Focus chain O [auth C] Focus chain R [auth D] Focus chain S [auth D]
BR Query on BR Download Ideal Coordinates CCD File SDF format, chain G [auth A] SDF format, chain H [auth A] SDF format, chain I [auth A] SDF format, chain J [auth A] SDF format, chain L [auth B] SDF format, chain M [auth B] SDF format, chain N [auth B] SDF format, chain P [auth C] SDF format, chain Q [auth C] SDF format, chain T [auth D] SDF format, chain U [auth D] MOL2 format, chain G [auth A] MOL2 format, chain H [auth A] MOL2 format, chain I [auth A] MOL2 format, chain J [auth A] MOL2 format, chain L [auth B] MOL2 format, chain M [auth B] MOL2 format, chain N [auth B] MOL2 format, chain P [auth C] MOL2 format, chain Q [auth C] MOL2 format, chain T [auth D] MOL2 format, chain U [auth D] mmCIF format, chain G [auth A] mmCIF format, chain H [auth A] mmCIF format, chain I [auth A] mmCIF format, chain J [auth A] mmCIF format, chain L [auth B] mmCIF format, chain M [auth B] mmCIF format, chain N [auth B] mmCIF format, chain P [auth C] mmCIF format, chain Q [auth C] mmCIF format, chain T [auth D] mmCIF format, chain U [auth D]	G [auth A] H [auth A] I [auth A] J [auth A] L [auth B] G [auth A], H [auth A], I [auth A], J [auth A], L [auth B], M [auth B], N [auth B], P [auth C], Q [auth C], T [auth D], U [auth D]	BROMIDE ION Br CPELXLSAUQHCOX-UHFFFAOYSA-M		Interactions Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain P [auth C] Focus chain Q [auth C] Focus chain T [auth D] Focus chain U [auth D] Interactions & Density Focus chain G [auth A] Focus chain H [auth A] Focus chain I [auth A] Focus chain J [auth A] Focus chain L [auth B] Focus chain M [auth B] Focus chain N [auth B] Focus chain P [auth C] Focus chain Q [auth C] Focus chain T [auth D] Focus chain U [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.60 Å
R-Value Free: 0.270
R-Value Work: 0.222
R-Value Observed: 0.224
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 46.571	α = 90
b = 100.492	β = 99.269
c = 111.01	γ = 90

Software Package:

Software Name	Purpose
PHENIX	refinement
XDS	data reduction
XDS	data scaling
PHASER	phasing

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History & Funding Information

Deposition Data

Released Date: 2019-02-27

Deposition Author(s):

Funding Organization	Location	Grant Number
Japan Agency for Medical Research and Development (AMED)	Japan	--

Revision History (Full details and data files)

Version 1.0: 2019-02-27
Type: Initial release
Version 1.1: 2023-11-22
Changes: Data collection, Database references, Refinement description
Version 1.2: 2024-10-16
Changes: Structure summary

Prepare Data

Validate Data

Deposit Data

Help and Resources

5ZQU

Crystal structure of tetrameric RXRalpha-LBD complexed with partial agonist CBt-PMN

Dual conformation of the ligand induces the partial agonistic activity of retinoid X receptor alpha (RXR alpha ).

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

Expand

Experimental Data

Structure Validation

Ligand Structure Quality Assessment

Deposition Data

Revision History (Full details and data files)