› 7sff

X-ray diffraction
2.05Å resolution

Human DNMT1(729-1600) Bound to Zebularine-Containing 12mer dsDNA and Inhibitor GSK3852279B

Released:
DOI: 10.2210/pdb7sff/pdb
PDB entry 7sff coloured by chain, front view.
PDB entry 7sff coloured by chain, side view.
PDB entry 7sff coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors.
Horton JR, Pathuri S, Wong K, Ren R, Rueda L, Fosbenner DT, Heerding DA, McCabe MT, Pappalardi MB, Zhang X, King BW, Cheng X
Structure 30 793-802.e5 (2022)
PMID: 35395178

Function and Biology Details

Reaction catalysed: 
S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine
Biochemical function:
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-121997 (preferred)
Entry contents:
1 distinct polypeptide molecule
2 distinct DNA molecules
Macromolecules (3 distinct):
DNA (cytosine-5)-methyltransferase 1 Chain: A
Molecule details ›
Chain: A
Length: 874 amino acids
Theoretical weight: 98.8 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P26358 (Residues: 729-1600; Coverage: 54%)
Gene names: AIM, CXXC9, DNMT, DNMT1
Sequence domains:
DNA (12-MER) Chain: C
Molecule details ›
Chain: C
Length: 12 nucleotides
Theoretical weight: 3.68 KDa
Source organism: Homo sapiens
Expression system: Not provided
DNA (12-MER) Chain: D
Molecule details ›
Chain: D
Length: 12 nucleotides
Theoretical weight: 3.67 KDa
Source organism: Homo sapiens
Expression system: Not provided

Ligands and Environments

4 bound ligands:
Ligand ZN 2 x ZN
Ligand EDO 7 x EDO
Ligand GOL 1 x GOL
Ligand C79 1 x C79
2 modified residues:
Ligand 5CM 1 x 5CM
Ligand PYO 1 x PYO

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 22-ID
Spacegroup: C2
Unit cell:
a: 161.72Å b: 78.237Å c: 117.061Å
α: 90° β: 125.928° γ: 90°
R-values:
R R work R free
0.182 0.182 0.217
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

2 review citations

Mediating and maintaining methylation while minimizing mutation: Recent advances on mammalian DNA methyltransferases.
Cheng et al. (2022)
1 more

1 mention without citation

Structural characterization of dicyanopyridine containing DNMT1-selective, non-nucleoside inhibitors.
Horton et al. (2022)