3E7C

Glucocorticoid Receptor LBD bound to GSK866

PDB DOI: https://doi.org/10.2210/pdb3E7C/pdb

Classification: TRANSCRIPTION
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2008-08-18 Released: 2008-11-25
Deposition Author(s): Madauss, K.P., Williams, S.P., Mclay, I., Stewart, E.L., Bledsoe, R.K.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.15 ?
R-Value Free: 0.266
R-Value Work: 0.210

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.6 of the entry. See complete history.

Literature

The first X-ray crystal structure of the glucocorticoid receptor bound to a non-steroidal agonist.

Madauss, K.P., Bledsoe, R.K., Mclay, I., Stewart, E.L., Uings, I.J., Weingarten, G., Williams, S.P.

(2008) Bioorg Med Chem Lett 18: 6097-6099

PubMed: 18952422 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2008.10.021
Primary Citation of Related Structures:
3E7C

PubMed Abstract:
The amino-pyrazole 2,6-dichloro-N-ethyl benzamide 1 is a selective GR agonist with dexamethasone-like in vitro potency. Its X-ray crystal structure in the GR LBD (Glucocorticoid ligand-binding domain) is described and compared to other reported structures of steroidal GR agonists in the GR LBD (3E7C).

Organizational Affiliation

Department of Computational and Structural Chemistry, Molecular Discovery Research, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. kevin.p.madauss@gsk.com

Macromolecule Content

Total Structure Weight: 63.78 kDa
Atom Count: 4,330
Modelled Residue Count: 514
Deposited Residue Count: 536
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Glucocorticoid receptor	A, C [auth B]	257	Homo sapiens	Mutation(s): 2 Gene Names: NR3C1, GRL
UniProt & NIH Common Fund Data Resources
Find proteins for P04150 (Homo sapiens) Explore P04150 Go to UniProtKB: P04150
PHAROS: P04150 GTEx: ENSG00000113580
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P04150
Sequence Annotations Expand
Reference Sequence

Find similar proteins by: Sequence | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Nuclear receptor coactivator 2	B [auth H], D	11	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for Q15596 (Homo sapiens) Explore Q15596 Go to UniProtKB: Q15596
PHAROS: Q15596 GTEx: ENSG00000140396
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q15596
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
866 Query on 866 Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain G [auth B] MOL2 format, chain E [auth A] MOL2 format, chain G [auth B] mmCIF format, chain E [auth A] mmCIF format, chain G [auth B]	E [auth A], G [auth B]	5-amino-N-[(2S)-2-({[(2,6-dichlorophenyl)carbonyl](ethyl)amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide C₂₃ H₂₁ Cl₂ F₄ N₅ O₃ LKQMULLPLYLIGW-QFIPXVFZSA-N		Interactions Focus chain E [auth A] Focus chain G [auth B] Interactions & Density Focus chain E [auth A] Focus chain G [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain F [auth A] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] mmCIF format, chain F [auth A] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B]	F [auth A], H [auth B], I [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain F [auth A] Focus chain H [auth B] Focus chain I [auth B]

Binding Affinity Annotations
ID	Source	Binding Affinity
866	BindingDB: 3E7C	IC50: 3.16 (nM) from 1 assay(s)
866	BindingDB: 3E7C	EC50: 2 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.15 ?
R-Value Free: 0.266
R-Value Work: 0.210
Space Group: P 6₁

Unit Cell:

Length ( ? )	Angle ( ? )
a = 126.654	α = 90
b = 126.654	β = 90
c = 78.991	γ = 120

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
PHASER	phasing
PHENIX	refinement
PDB_EXTRACT	data extraction
StructureStudio	data collection
HKL-2000	data reduction
HKL-2000	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2008-11-25

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2008-11-25
Type: Initial release
Version 1.1: 2011-07-13
Changes: Non-polymer description, Version format compliance
Version 1.2: 2014-04-02
Changes: Source and taxonomy
Version 1.3: 2017-10-25
Changes: Refinement description
Version 1.4: 2021-10-20
Changes: Database references, Derived calculations
Version 1.5: 2024-02-21
Changes: Data collection
Version 1.6: 2024-04-03
Changes: Refinement description