2RFI

Crystal structure of catalytic domain of human euchromatic histone methyltransferase 1 in complex with SAH and dimethylated H3K9 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.59 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural biology of human H3K9 methyltransferases

Wu, H.Min, J.Lunin, V.V.Antoshenko, T.Dombrovski, L.Zeng, H.Allali-Hassani, A.Campagna-Slater, V.Vedadi, M.Arrowsmith, C.H.Plotnikov, A.N.Schapira, M.

(2010) PLoS One 5: e8570-e8570

  • DOI: https://doi.org/10.1371/journal.pone.0008570
  • Primary Citation of Related Structures:  
    2IGQ, 2O8J, 2QPW, 2R3A, 2RFI, 3HNA

  • PubMed Abstract: 

    SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity.


  • Organizational Affiliation

    Structural Genomics Consortium, University of Toronto, Toronto, Ontario, Canada.


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: EHMT1EUHMTASE1KIAA1876
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
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Histone H3C [auth P],
D [auth Q]
11N/AMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH
Query on SAH

Download Ideal Coordinates CCD File 
I [auth A],
J [auth A]
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]
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
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MLY
Query on MLY
C [auth P],
D [auth Q]
L-PEPTIDE LINKINGC8 H18 N2 O2LYS
Binding Affinity Annotations 
IDSourceBinding Affinity
SAH BindingDB:  2RFI IC50: 230 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.59 Å
  • R-Value Free: 0.220 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.593α = 90
b = 85.627β = 90
c = 95.67γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2007-10-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description