3QOW

DOT1L Structure in complex with SAM


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.162 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Chemogenetic analysis of human protein methyltransferases.

Richon, V.M.Johnston, D.Sneeringer, C.J.Jin, L.Majer, C.R.Elliston, K.Jerva, L.F.Scott, M.P.Copeland, R.A.

(2011) Chem Biol Drug Des 78: 199-210

  • DOI: https://doi.org/10.1111/j.1747-0285.2011.01135.x
  • Primary Citation of Related Structures:  
    3QOW, 3QOX

  • PubMed Abstract: 

    A survey of the human genome was performed to understand the constituency of protein methyltransferases (both protein arginine and lysine methyltransferases) and the relatedness of their catalytic domains. We identified 51 protein lysine methyltransferase proteins based on similarity to the canonical Drosophila Su(var)3-9, enhancer of zeste (E(z)), and trithorax (trx) domain. Disruptor of telomeric silencing-1-like, a known protein lysine methyltransferase, did not fit within the protein lysine methyltransferase family, but did group with the protein arginine methyltransferases, along with 44 other proteins, including the METTL and NOP2/Sun domain family proteins. We show that a representative METTL, METTL11A, demonstrates catalytic activity as a histone methyltransferase. We also solved the co-crystal structures of disruptor of telomeric silencing-1-like with S-adenosylmethionine and S-adenosylhomocysteine bound in its active site. The conformation of both ligands is virtually identical to that found in known protein arginine methyltransferases, METTL and NOP2/Sun domain family proteins and is distinct from that seen in the Drosophila Su(var)3-9, enhancer of zeste (E(z)), and trithorax (trx) domain protein lysine methyltransferases. We have developed biochemical assays for 11 members of the protein methyltransferase target class and have profiled the affinity of three ligands for these enzymes: the common methyl-donating substrate S-adenosylmethionine; the common reaction product S-adenosylhomocysteine; and the natural product sinefungin. The affinity of each of these ligands is mapped onto the family trees of the protein lysine methyltransferases and protein arginine methyltransferases to reveal patterns of ligand recognition by these enzymes.


  • Organizational Affiliation

    Epizyme, Inc., 840 Memorial Drive, Cambridge, MA 02139, USA Genstruct Inc., One Alewife Center, Cambridge, MA 02140, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Histone-lysine N-methyltransferase426Homo sapiensMutation(s): 0 
Gene Names: DOT1LKIAA1814KMT4
EC: 2.1.1.43
UniProt & NIH Common Fund Data Resources
Find proteins for Q8TEK3 (Homo sapiens)
Explore Q8TEK3 
Go to UniProtKB:  Q8TEK3
PHAROS:  Q8TEK3
GTEx:  ENSG00000104885 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8TEK3
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.192 
  • R-Value Work: 0.160 
  • R-Value Observed: 0.162 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 153.204α = 90
b = 153.204β = 90
c = 51.314γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2011-05-25 
  • Deposition Author(s): Jin, L.

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-25
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-08-10
    Changes: Database references
  • Version 1.3: 2024-02-21
    Changes: Data collection, Database references, Derived calculations