3ZR7

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 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 Biol Chem 286: 35079-35086

  • 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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROGESTERONE RECEPTOR
A, B
260Homo sapiensMutation(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 Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06401
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
OR8
Query on OR8

Download Ideal Coordinates CCD File 
C [auth A],
J [auth B]
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
SO4
Query on SO4

Download Ideal Coordinates CCD File 
E [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
D [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
D [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
K [auth B],
L [auth B],
M [auth B],
N [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.65 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.792α = 90
b = 64.235β = 95.67
c = 69.981γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

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