4Y2H

Crystal structure of human protein arginine methyltransferase PRMT6 bound to SAH and an aryl pyrazole inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.37 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 

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Literature

Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound.

Mitchell, L.H., Drew, A.E., Ribich, S.A., Rioux, N., Swinger, K.K., Jacques, S.L., Lingaraj, T., Boriack-Sjodin, P.A., Waters, N.J., Wigle, T.J., Moradei, O., Jin, L., Riera, T., Porter-Scott, M., Moyer, M.P., Smith, J.J., Chesworth, R., Copeland, R.A.

(2015) ACS Med Chem Lett 6: 655-659

  • DOI: https://doi.org/10.1021/acsmedchemlett.5b00071
  • Primary Citation of Related Structures:  
    4Y2H, 4Y30

  • PubMed Abstract: 

    A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent, selective, small molecule PRMT6 inhibitor tool compound, EPZ020411. PRMT6 overexpression has been reported in several cancer types suggesting that inhibition of PRMT6 activity may have therapeutic utility. Identification of EPZ020411 provides the field with the first small molecule tool compound for target validation studies. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies.

    • Organizational Affiliation: 

    Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein arginine N-methyltransferase 6
A, B
352Homo sapiensMutation(s): 0 
Gene Names: PRMT6, HRMT1L6
EC: 2.1.1 (PDB Primary Data), 2.1.1.125 (PDB Primary Data), 2.1.1.319 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q96LA8 (Homo sapiens)
Explore Q96LA8 
Go to UniProtKB:  Q96LA8
PHAROS:  Q96LA8
GTEx:  ENSG00000198890 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96LA8
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
49K BindingDB:  4Y2H IC50: 11 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.37 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 
  • Space Group: P 43
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.97α = 90
b = 99.97β = 90
c = 89.49γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
Aimlessdata scaling
PDB_EXTRACTdata extraction
XDSdata scaling
REFMACphasing

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: 2015-04-22
    Type: Initial release
  • Version 1.1: 2015-07-08
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Derived calculations, Refinement description, Source and taxonomy
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references