3AV4

Crystal structure of mouse DNA methyltransferase 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.232 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).

Takeshita, K.Suetake, I.Yamashita, E.Suga, M.Narita, H.Nakagawa, A.Tajima, S.

(2011) Proc Natl Acad Sci U S A 108: 9055-9059

  • DOI: https://doi.org/10.1073/pnas.1019629108
  • Primary Citation of Related Structures:  
    3AV4, 3AV5, 3AV6

  • PubMed Abstract: 

    Methylation of cytosine in DNA plays a crucial role in development through inheritable gene silencing. The DNA methyltransferase Dnmt1 is responsible for the propagation of methylation patterns to the next generation via its preferential methylation of hemimethylated CpG sites in the genome; however, how Dnmt1 maintains methylation patterns is not fully understood. Here we report the crystal structure of the large fragment (291-1620) of mouse Dnmt1 and its complexes with cofactor S-adenosyl-L-methionine and its product S-adenosyl-L-homocystein. Notably, in the absence of DNA, the N-terminal domain responsible for targeting Dnmt1 to replication foci is inserted into the DNA-binding pocket, indicating that this domain must be removed for methylation to occur. Upon binding of S-adenosyl-L-methionine, the catalytic cysteine residue undergoes a conformation transition to a catalytically competent position. For the recognition of hemimethylated DNA, Dnmt1 is expected to utilize a target recognition domain that overhangs the putative DNA-binding pocket. Taking into considerations the recent report of a shorter fragment structure of Dnmt1 that the CXXC motif positions itself in the catalytic pocket and prevents aberrant de novo methylation, we propose that maintenance methylation is a multistep process accompanied by structural changes.


  • Organizational Affiliation

    Laboratory of Supramolecular Crystallography, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA (cytosine-5)-methyltransferase 11,330Mus musculusMutation(s): 0 
Gene Names: Dnmt1DnmtMet1Uim
EC: 2.1.1.37
UniProt
Find proteins for P13864 (Mus musculus)
Explore P13864 
Go to UniProtKB:  P13864
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP13864
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.232 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 135.78α = 90
b = 97.865β = 90
c = 130.636γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction
SHARPphasing
BUSTERrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-04
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-06-27
    Changes: Experimental preparation
  • Version 1.3: 2019-12-25
    Changes: Database references
  • Version 1.4: 2024-03-13
    Changes: Data collection, Database references, Derived calculations