4NVQ

Human G9a in Complex with Inhibitor A-366

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.03 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 

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Ligand Structure Quality Assessment 


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


Literature

Discovery and development of potent and selective inhibitors of histone methyltransferase g9a.

Sweis, R.F., Pliushchev, M., Brown, P.J., Guo, J., Li, F., Maag, D., Petros, A.M., Soni, N.B., Tse, C., Vedadi, M., Michaelides, M.R., Chiang, G.G., Pappano, W.N.

(2014) ACS Med Chem Lett 5: 205-209

  • DOI: https://doi.org/10.1021/ml400496h
  • Primary Citation of Related Structures:  
    4NVQ

  • PubMed Abstract: 

    G9a is a histone lysine methyltransferase responsible for the methylation of histone H3 lysine 9. The discovery of A-366 arose from a unique diversity screening hit, which was optimized by incorporation of a propyl-pyrrolidine subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other methyltransferases.

    • Organizational Affiliation: 

    Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone-lysine N-methyltransferase EHMT2
A, B
285Homo sapiensMutation(s): 0 
Gene Names: EHMT2, BAT8, C6orf30, G9A, KMT1C, NG36
EC: 2.1.1 (PDB Primary Data), 2.1.1.43 (PDB Primary Data), 2.1.1.367 (UniProt)
UniProt & NIH Common Fund Data Resources
Find proteins for Q96KQ7 (Homo sapiens)
Explore Q96KQ7 
Go to UniProtKB:  Q96KQ7
PHAROS:  Q96KQ7
GTEx:  ENSG00000204371 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96KQ7
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH
Query on SAH
Download Ideal Coordinates CCD File 
D [auth A],
I [auth B]		S-ADENOSYL-L-HOMOCYSTEINE
C14 H20 N6 O5 S
ZJUKTBDSGOFHSH-WFMPWKQPSA-N
2OD
Query on 2OD
Download Ideal Coordinates CCD File 
C [auth A],
J [auth B]		5'-methoxy-6'-[3-(pyrrolidin-1-yl)propoxy]spiro[cyclobutane-1,3'-indol]-2'-amine
C19 H27 N3 O2
BKCDJTRMYWSXMC-UHFFFAOYSA-N
ZN
Query on ZN
Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
K [auth B]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
K [auth B],
L [auth B],
M [auth B],
N [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.03 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.203 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.14α = 90
b = 78.25β = 92.61
c = 71.44γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
JDirectordata collection
autoPROCdata scaling
PHASERphasing
BUSTERrefinement

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: 2014-01-15
    Type: Initial release
  • Version 1.1: 2014-07-16
    Changes: Database references
  • Version 1.2: 2017-11-22
    Changes: Refinement description
  • Version 1.3: 2024-02-28
    Changes: Data collection, Database references, Derived calculations, Refinement description