3MO0

Human G9a-like (GLP, also known as EHMT1) in complex with inhibitor E11


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.78 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases.

Chang, Y.Ganesh, T.Horton, J.R.Spannhoff, A.Liu, J.Sun, A.Zhang, X.Bedford, M.T.Shinkai, Y.Snyder, J.P.Cheng, X.

(2010) J Mol Biol 400: 1-7

  • DOI: https://doi.org/10.1016/j.jmb.2010.04.048
  • Primary Citation of Related Structures:  
    3MO0, 3MO2, 3MO5

  • PubMed Abstract: 

    Dynamic histone lysine methylation involves the activities of modifying enzymes (writers), enzymes removing modifications (erasers), and readers of the histone code. One common feature of these activities is the recognition of lysines in methylated and unmethylated states, whether they are substrates, reaction products, or binding partners. We applied the concept of adding a lysine mimic to an established inhibitor (BIX-01294) of histone H3 lysine 9 methyltransferases G9a and G9a-like protein by including a 5-aminopentyloxy moiety, which is inserted into the target lysine-binding channel and becomes methylated by G9a-like protein, albeit slowly. The compound enhances its potency in vitro and reduces cell toxicity in vivo. We suggest that adding a lysine or methyl-lysine mimic should be considered in the design of small-molecule inhibitors for other methyl-lysine writers, erasers, and readers.


  • Organizational Affiliation

    Department of Biochemistry, Emory University, Atlanta, GA 30322, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone-lysine N-methyltransferase, H3 lysine-9 specific 5
A, B
285Homo sapiensMutation(s): 0 
Gene Names: EHMT1EUHMTASE1KIAA1876KMT1D
EC: 2.1.1.43
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H9B1 (Homo sapiens)
Explore Q9H9B1 
Go to UniProtKB:  Q9H9B1
PHAROS:  Q9H9B1
GTEx:  ENSG00000181090 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9H9B1
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
E11
Query on E11

Download Ideal Coordinates CCD File 
D [auth A],
J [auth A],
N [auth B]
N~4~-(1-benzylpiperidin-4-yl)-N~2~-[3-(dimethylamino)propyl]-6,7-dimethoxyquinazoline-2,4-diamine
C27 H38 N6 O2
YYFDMPHIONBOKZ-UHFFFAOYSA-N
SAH
Query on SAH

Download Ideal Coordinates CCD File 
C [auth A],
M [auth B]
S-ADENOSYL-L-HOMOCYSTEINE
C14 H20 N6 O5 S
ZJUKTBDSGOFHSH-WFMPWKQPSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
O [auth B],
P [auth B],
Q [auth B],
R [auth B],
S [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
K [auth B],
L [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
E11 PDBBind:  3MO0 Kd: 154 (nM) from 1 assay(s)
SAH BindingDB:  3MO0 IC50: 230 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.78 Å
  • R-Value Free: 0.306 
  • R-Value Work: 0.225 
  • R-Value Observed: 0.225 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.3α = 90
b = 94.5β = 90
c = 138.2γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-06-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description