5IZ0

RORgamma in complex with agonist BIO592 and Coactivator EBI96

PDB DOI: https://doi.org/10.2210/pdb5IZ0/pdb

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

Deposited: 2016-03-24 Released: 2016-06-15
Deposition Author(s): Marcotte, D.J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.63 Å
R-Value Free: 0.255
R-Value Work: 0.199
R-Value Observed: 0.202

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand.

Marcotte, D.J., Liu, Y., Little, K., Jones, J.H., Powell, N.A., Wildes, C.P., Silvian, L.F., Chodaparambil, J.V.

(2016) BMC Struct Biol 16: 7-7

PubMed: 27246200 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1186/s12900-016-0059-3
Primary Citation of Related Structures:
5IXK, 5IZ0

PubMed Abstract:
The nuclear hormone receptor RORγ regulates transcriptional genes involved in the production of the pro-inflammatory interleukin IL-17 which has been linked to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. This transcriptional activity of RORγ is modulated through a protein-protein interaction involving the activation function 2 (AF2) helix on the ligand binding domain of RORγ and a conserved LXXLL helix motif on coactivator proteins. Our goal was to develop a RORγ specific inverse agonist that would help down regulate pro-inflammatory gene transcription by disrupting the protein protein interaction with coactivator proteins as a therapeutic agent.

Organizational Affiliation

Chemical and Molecular Therapeutics, Biogen Inc, 250 Binney Street, Cambridge, MA, 02142, USA. doug.marcotte@biogenidec.com.

Macromolecule Content

Total Structure Weight: 130.76 kDa
Atom Count: 8,532
Modelled Residue Count: 1,017
Deposited Residue Count: 1,112
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Nuclear receptor ROR-gamma	A, C [auth B], E [auth D], G	263	Homo sapiens	Mutation(s): 0 Gene Names: RORC, NR1F3, RORG, RZRG
UniProt & NIH Common Fund Data Resources
Find proteins for P51449 (Homo sapiens) Explore P51449 Go to UniProtKB: P51449
PHAROS: P51449 GTEx: ENSG00000143365
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P51449
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
GLU-PHE-PRO-TYR-LEU-LEU-SER-LEU-LEU-GLY-GLU-VAL-SER-PRO-GLN	B [auth C], D [auth E], F, H	15	Homo sapiens	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
6F1 Query on 6F1 Download Ideal Coordinates CCD File SDF format, chain I [auth A] SDF format, chain R [auth B] SDF format, chain Y [auth D] SDF format, chain DA [auth G] MOL2 format, chain I [auth A] MOL2 format, chain R [auth B] MOL2 format, chain Y [auth D] MOL2 format, chain DA [auth G]	DA [auth G], I [auth A], R [auth B], Y [auth D]	N-(4-ethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-3,4-dimethyl-N-(2,2,2-trifluoroethyl)benzene-1-sulfonamide C₂₀ H₂₁ F₃ N₂ O₄ S LODXRGHOWOQXTP-UHFFFAOYSA-N		Interactions Focus chain DA [auth G] Focus chain I [auth A] Focus chain R [auth B] Focus chain Y [auth D] Interactions & Density Focus chain DA [auth G] Focus chain I [auth A] Focus chain R [auth B] Focus chain Y [auth D]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain AA [auth D] SDF format, chain BA [auth D] SDF format, chain CA [auth D] SDF format, chain EA [auth G] SDF format, chain FA [auth G] SDF format, chain GA [auth G] SDF format, chain HA [auth G] SDF format, chain IA [auth G] SDF format, chain J [auth A] SDF format, chain K [auth A] SDF format, chain M [auth A] SDF format, chain N [auth A] SDF format, chain P [auth A] SDF format, chain Q [auth A] SDF format, chain T [auth B] SDF format, chain U [auth B] SDF format, chain V [auth B] SDF format, chain W [auth B] SDF format, chain X [auth B] SDF format, chain Z [auth D] SDF format, chain L [auth A] SDF format, chain O [auth A] SDF format, chain S [auth B] MOL2 format, chain AA [auth D] MOL2 format, chain BA [auth D] MOL2 format, chain CA [auth D] MOL2 format, chain EA [auth G] MOL2 format, chain FA [auth G] MOL2 format, chain GA [auth G] MOL2 format, chain HA [auth G] MOL2 format, chain IA [auth G] MOL2 format, chain J [auth A] MOL2 format, chain K [auth A] MOL2 format, chain M [auth A] MOL2 format, chain N [auth A] MOL2 format, chain P [auth A] MOL2 format, chain Q [auth A] MOL2 format, chain T [auth B] MOL2 format, chain U [auth B] MOL2 format, chain V [auth B] MOL2 format, chain W [auth B] MOL2 format, chain X [auth B] MOL2 format, chain Z [auth D] MOL2 format, chain L [auth A] MOL2 format, chain O [auth A] MOL2 format, chain S [auth B]	AA [auth D] BA [auth D] CA [auth D] EA [auth G] FA [auth G] AA [auth D], BA [auth D], CA [auth D], EA [auth G], FA [auth G], GA [auth G], HA [auth G], IA [auth G], J [auth A], K [auth A], L [auth A], M [auth A], N [auth A], O [auth A], P [auth A], Q [auth A], S [auth B], T [auth B], U [auth B], V [auth B], W [auth B], X [auth B], Z [auth D]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain AA [auth D] Focus chain BA [auth D] Focus chain CA [auth D] Focus chain EA [auth G] Focus chain FA [auth G] Focus chain GA [auth G] Focus chain HA [auth G] Focus chain IA [auth G] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Z [auth D] Interactions & Density Focus chain AA [auth D] Focus chain BA [auth D] Focus chain CA [auth D] Focus chain EA [auth G] Focus chain FA [auth G] Focus chain GA [auth G] Focus chain HA [auth G] Focus chain IA [auth G] Focus chain J [auth A] Focus chain K [auth A] Focus chain L [auth A] Focus chain M [auth A] Focus chain N [auth A] Focus chain O [auth A] Focus chain P [auth A] Focus chain Q [auth A] Focus chain S [auth B] Focus chain T [auth B] Focus chain U [auth B] Focus chain V [auth B] Focus chain W [auth B] Focus chain X [auth B] Focus chain Z [auth D]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.63 Å
R-Value Free: 0.255
R-Value Work: 0.199
R-Value Observed: 0.202
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 85.672	α = 90
b = 68.111	β = 109.9
c = 96.056	γ = 90

Software Package:

Software Name	Purpose
SCALA	data scaling
REFMAC	refinement
PDB_EXTRACT	data extraction
MOLREP	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2016-06-15

Deposition Author(s):

Marcotte, D.J.

Revision History (Full details and data files)

Version 1.0: 2016-06-15
Type: Initial release
Version 1.1: 2023-09-27
Changes: Data collection, Database references, Derived calculations, Refinement description

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Help and Resources

5IZ0

RORgamma in complex with agonist BIO592 and Coactivator EBI96

Structural determinant for inducing RORgamma specific inverse agonism triggered by a synthetic benzoxazinone ligand.

Entity ID: 1

UniProt & NIH Common Fund Data Resources

Entity Groups

Sequence Annotations

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Entity ID: 2