3PT6

Crystal structure of mouse DNMT1(650-1602) in complex with DNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.213 

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Literature

Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation.

Song, J.Rechkoblit, O.Bestor, T.H.Patel, D.J.

(2011) Science 331: 1036-1040

  • DOI: https://doi.org/10.1126/science.1195380
  • Primary Citation of Related Structures:  
    3PT6, 3PT9, 3PTA

  • PubMed Abstract: 

    Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse and human DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2), and methyltransferase domains bound to DNA-containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, in which unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.


  • Organizational Affiliation

    Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA (cytosine-5)-methyltransferase 1A,
F [auth B]
954Mus 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
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*TP*CP*CP*CP*GP*TP*GP*AP*GP*CP*CP*TP*CP*CP*GP*CP*AP*GP*G)-3')B [auth C],
D
19N/A
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
DNA (5'-D(*CP*CP*TP*GP*CP*GP*GP*AP*GP*GP*CP*TP*CP*AP*CP*GP*GP*GP*A)-3')C [auth I],
E [auth J]
19N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH
Query on SAH

Download Ideal Coordinates CCD File 
G [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 
H [auth A]
I [auth A]
J [auth A]
K [auth A]
L [auth B]
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth B],
N [auth B],
O [auth B],
P [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SAH BindingDB:  3PT6 IC50: min: 71, max: 4000 (nM) from 8 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.266 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.213 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.192α = 90
b = 213.507β = 99.64
c = 86.274γ = 90
Software Package:
Software NamePurpose
MAR345dtbdata collection
SHARPphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2024-02-21
    Changes: Data collection, Database references, Derived calculations