7NFB

ER-PRS*(+) (Y537S) in complex with genistein and SRC-2 coactivator peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.33 Å
  • R-Value Free: 0.178 
  • R-Value Work: 0.142 
  • R-Value Observed: 0.143 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A PROSS-designed extensively mutated estrogen receptor alpha variant displays enhanced thermal stability while retaining native allosteric regulation and structure.

Kriegel, M.Wiederanders, H.J.Alkhashrom, S.Eichler, J.Muller, Y.A.

(2021) Sci Rep 11: 10509-10509

  • DOI: https://doi.org/10.1038/s41598-021-89785-1
  • Primary Citation of Related Structures:  
    7NDO, 7NEL, 7NFB

  • PubMed Abstract: 

    Protein stability limitations often hamper the exploration of proteins as drug targets. Here, we show that the application of PROSS server algorithms to the ligand-binding domain of human estrogen receptor alpha (hERα) enabled the development of variant ER PRS* that comprises 24 amino acid substitutions and exhibits multiple improved characteristics. The protein displays enhanced production rates in E. coli, crystallizes readily and its thermal stability is increased significantly by 23 °C. hERα is a nuclear receptor (NR) family member. In NRs, protein function is allosterically regulated by its interplay with small molecule effectors and the interaction with coregulatory proteins. The in-depth characterization of ER PRS* shows that these cooperative effects are fully preserved despite that 10% of all residues were substituted . Crystal structures reveal several salient features, i.e. the introduction of a tyrosine corner in a helix-loop-helix segment and the formation of a novel surface salt bridge network possibly explaining the enhanced thermal stability. ER PRS* shows that prior successes in computational approaches for stabilizing proteins can be extended to proteins with complex allosteric regulatory behaviors as present in NRs. Since NRs including hERα are implicated in multiple diseases, our ER PRS* variant shows significant promise for facilitating the development of novel hERα modulators.


  • Organizational Affiliation

    Division of Biotechnology, Department of Biology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Estrogen receptor
A, B
247Homo sapiensMutation(s): 28 
Gene Names: ESR1ESRNR3A1
UniProt & NIH Common Fund Data Resources
Find proteins for P03372 (Homo sapiens)
Explore P03372 
Go to UniProtKB:  P03372
PHAROS:  P03372
GTEx:  ENSG00000091831 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03372
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor coactivator 2
C, D
15Homo sapiensMutation(s): 1 
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 Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15596
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GEN (Subject of Investigation/LOI)
Query on GEN

Download Ideal Coordinates CCD File 
E [auth A],
P [auth B]
GENISTEIN
C15 H10 O5
TZBJGXHYKVUXJN-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
CA [auth C]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
H [auth A]
I [auth A]
J [auth A]
K [auth A]
L [auth A]
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
R [auth B],
S [auth B],
T [auth B],
U [auth B],
V [auth B],
W [auth B],
X [auth B],
Y [auth B],
Z [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
AA [auth B],
BA [auth B],
O [auth A]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
NA
Query on NA

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
Q [auth B]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.33 Å
  • R-Value Free: 0.178 
  • R-Value Work: 0.142 
  • R-Value Observed: 0.143 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.854α = 90
b = 81.526β = 108.459
c = 58.464γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MxCuBEdata collection
PHASERphasing
XDSdata processing
XDSdata reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2021-08-25
    Type: Initial release
  • Version 1.1: 2022-10-26
    Changes: Derived calculations
  • Version 1.2: 2024-01-31
    Changes: Data collection, Refinement description