3EPZ

Structure of the replication foci-targeting sequence of human DNA cytosine methyltransferase DNMT1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.31 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.216 

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This is version 1.3 of the entry. See complete history


Literature

The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1.

Syeda, F.Fagan, R.L.Wean, M.Avvakumov, G.V.Walker, J.R.Xue, S.Dhe-Paganon, S.Brenner, C.

(2011) J Biol Chem 286: 15344-15351

  • DOI: https://doi.org/10.1074/jbc.M110.209882
  • Primary Citation of Related Structures:  
    3EPZ

  • PubMed Abstract: 

    Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome. The N-terminal replication focus targeting sequence (RFTS) domain of Dnmt1 has been implicated in subcellular localization, protein association, and catalytic function. However, progress in understanding its function has been limited by the lack of assays for and a structure of this domain. Here, we show that the naked DNA- and polynucleosome-binding activities of Dnmt1 are inhibited by the RFTS domain, which functions by virtue of binding the catalytic domain to the exclusion of DNA. Kinetic analysis with a fluorogenic DNA substrate established the RFTS domain as a 600-fold inhibitor of Dnmt1 enzymatic activity. The crystal structure of the RFTS domain reveals a novel fold and supports a mechanism in which an RFTS-targeted Dnmt1-binding protein, such as Uhrf1, may activate Dnmt1 for DNA binding.


  • Organizational Affiliation

    Structural Genomics Consortium and Department of Physiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA (cytosine-5)-methyltransferase 1
A, B
268Homo sapiensMutation(s): 0 
Gene Names: AIMCXX9CXXC9DNMTDNMT1
EC: 2.1.1.37
UniProt & NIH Common Fund Data Resources
Find proteins for P26358 (Homo sapiens)
Explore P26358 
Go to UniProtKB:  P26358
PHAROS:  P26358
GTEx:  ENSG00000130816 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26358
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.31 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.216 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.544α = 90
b = 59.768β = 92.31
c = 96.286γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SOLVEphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-11-25
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2011-09-14
    Changes: Database references
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary