3ZRB | pdb_00003zrb

Structural basis for agonism and antagonism for a set of chemically related progesterone receptor modulators

PDB DOI: https://doi.org/10.2210/pdb3ZRB/pdb

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

Deposited: 2011-06-15 Released: 2011-08-17
Deposition Author(s): Lusher, S.J., Raaijmakers, H.C.A., Vu-Pham, D., Dechering, K., Wai Lam, T., Brown, A.R., Hamilton, N.M., Nimz, O., Azevedo, R., Mcguire, R., Oubrie, A., de Vlieg, J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free:
0.221 (Depositor), 0.240 (DCC)
R-Value Work:
0.184 (Depositor), 0.200 (DCC)

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

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

Literature

Structural basis for agonism and antagonism for a set of chemically related progesterone receptor modulators.

Lusher, S.J., Raaijmakers, H.C., Vu-Pham, D., Dechering, K., Lam, T.W., Brown, A.R., Hamilton, N.M., Nimz, O., Bosch, R., McGuire, R., Oubrie, A., de Vlieg, J.

(2011) J Biological Chem 286: 35079-35086

PubMed: 21849509 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1074/jbc.M111.273029
Primary Citation of Related Structures:
3ZR7, 3ZRA, 3ZRB

PubMed Abstract:
The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixed profiles inbetween. We describe here two new progesterone receptor ligand binding domain x-ray structures bound to compounds from a structurally related but functionally divergent series, which show different binding modes corresponding to their agonistic or antagonistic nature. In addition, we present a third progesterone receptor ligand binding domain dimer bound to an agonist in monomer A and an antagonist in monomer B, which display binding modes in agreement with the earlier observation that agonists and antagonists from this series adopt different binding modes.

Organizational Affiliation

Department of Molecular Design and Informatics, DMPK, MSD, PO Box 20, 5340 BH Oss, The Netherlands. scott.lusher@merck.com

Macromolecule Content

Total Structure Weight: 61.17 kDa
Atom Count: 4,384
Modelled Residue Count: 500
Deposited Residue Count: 520
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
PROGESTERONE RECEPTOR	A, B	260	Homo sapiens	Mutation(s): 0
UniProt & NIH Common Fund Data Resources
Find proteins for P06401 (Homo sapiens) Explore P06401 Go to UniProtKB: P06401
PHAROS: P06401 GTEx: ENSG00000082175
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P06401
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 4 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
OR8 Query on OR8 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]	2-CHLORO-N-[[4-(3,5-DIMETHYLISOXAZOL-4-YL)PHENYL]METHYL]-1,4-DIMETHYL-1H-PYRAZOLE-4-SULFONAMIDE C₁₇ H₁₉ Cl N₄ O₃ S XNTNHEPWXKNVBH-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
ORC Query on ORC Download Ideal Coordinates CCD File SDF format, chain H [auth B] MOL2 format, chain H [auth B] mmCIF format, chain H [auth B]	H [auth B]	(R)-N-[1-[4-(3,5-DIMETHYLISOXAZOL-4-YL)PHENYL]ETHYL]-3,5-DIMETHYLISOXAZOLE-4-SULFONAMIDE C₁₈ H₂₁ N₃ O₄ S QXPXDFCURRGQGI-SNVBAGLBSA-N		Interactions Focus chain H [auth B] Interactions & Density Focus chain H [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A] mmCIF format, chain D [auth A]	D [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain I [auth B] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain I [auth B] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain I [auth B]	E [auth A], F [auth A], G [auth A], I [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth B] Interactions & Density Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth B]

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 1.80 Å
R-Value Free: 0.221 (Depositor), 0.240 (DCC)
R-Value Work: 0.184 (Depositor), 0.200 (DCC)

Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 56.252	α = 90
b = 64.057	β = 96.62
c = 69.691	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
MOSFLM	data reduction
SCALEPACK	data scaling

Structure Validation

View Full Validation Report

Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2011-08-17

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2011-08-17
Type: Initial release
Version 1.1: 2011-10-26
Changes: Database references
Version 1.2: 2017-12-27
Changes: Database references, Structure summary
Version 1.3: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Other