5EMJ

Crystal structure of PRMT5:MEP50 with Compound 8 and sinefungin

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.27 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 

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Literature

Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666.

Duncan, K.W., Rioux, N., Boriack-Sjodin, P.A., Munchhof, M.J., Reiter, L.A., Majer, C.R., Jin, L., Johnston, L.D., Chan-Penebre, E., Kuplast, K.G., Porter Scott, M., Pollock, R.M., Waters, N.J., Smith, J.J., Moyer, M.P., Copeland, R.A., Chesworth, R.

(2016) ACS Med Chem Lett 7: 162-166

  • DOI: https://doi.org/10.1021/acsmedchemlett.5b00380
  • Primary Citation of Related Structures:  
    5EMJ, 5EMK, 5EML, 5EMM

  • PubMed Abstract: 

    The recent publication of a potent and selective inhibitor of protein methyltransferase 5 (PRMT5) provides the scientific community with in vivo-active tool compound EPZ015666 (GSK3235025) to probe the underlying pharmacology of this key enzyme. Herein, we report the design and optimization strategies employed on an initial hit compound with poor in vitro clearance to yield in vivo tool compound EPZ015666 and an additional potent in vitro tool molecule EPZ015866 (GSK3203591).

    • Organizational Affiliation: 

    Epizyme, Inc. , 400 Technology Square, Cambridge, Massachusetts 02139, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein arginine N-methyltransferase 5645Homo sapiensMutation(s): 0 
Gene Names: PRMT5, HRMT1L5, IBP72, JBP1, SKB1
EC: 2.1.1 (PDB Primary Data), 2.1.1.125 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for O14744 (Homo sapiens)
Explore O14744 
Go to UniProtKB:  O14744
PHAROS:  O14744
GTEx:  ENSG00000100462 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO14744
Sequence Annotations
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  • Reference Sequence
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Methylosome protein 50350Homo sapiensMutation(s): 0 
Gene Names: WDR77, MEP50, WD45, HKMT1069, Nbla10071
UniProt & NIH Common Fund Data Resources
Find proteins for Q9BQA1 (Homo sapiens)
Explore Q9BQA1 
Go to UniProtKB:  Q9BQA1
PHAROS:  Q9BQA1
GTEx:  ENSG00000116455 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BQA1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
5QJ BindingDB:  5EMJ IC50: min: 33, max: 180 (nM) from 3 assay(s)
Binding MOAD:  5EMJ IC50: 33 (nM) from 1 assay(s)
SFG BindingDB:  5EMJ IC50: 8600 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.27 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.24α = 90
b = 138.83β = 90
c = 179.34γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
iMOSFLMdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-02-24
    Type: Initial release
  • Version 1.1: 2016-07-27
    Changes: Data collection
  • Version 1.2: 2018-04-18
    Changes: Data collection, Database references, Derived calculations