4DA4

Structure of mouse DNMT1 (731-1602) bound to hemimethylated CpG DNA

Summary for 4DA4

• Entry DOI: 10.2210/pdb4da4/pdb
• Descriptor: DNA (cytosine-5)-methyltransferase 1, DNA_UPPER_STRAND, DNA_LOWER_STRAND, ... (7 entities in total)
• Functional Keywords: maintenance dna methylation, covalent complex, transferase-dna complex, transferase/dna
• Biological source: Mus musculus (mouse); More
• Cellular location: Nucleus: P13864
• Total number of polymer chains: 6
• Total formula weight: 213997.43

Authors

Song, J.,Patel, D.J. (deposition date: 2012-01-12, release date: 2012-02-22, Last modification date: 2024-02-28)

Primary citation

Song, J.,Teplova, M.,Ishibe-Murakami, S.,Patel, D.J.
Structure-Based Mechanistic Insights into DNMT1-Mediated Maintenance DNA Methylation.
Science, 335:709-712, 2012

PubMed Abstract: DNMT1, the major maintenance DNA methyltransferase in animals, helps to regulate gene expression, genome imprinting, and X-chromosome inactivation. We report on the crystal structure of a productive covalent mouse DNMT1(731-1602)-DNA complex containing a central hemimethylated CpG site. The methyl group of methylcytosine is positioned within a shallow hydrophobic concave surface, whereas the cytosine on the target strand is looped out and covalently anchored within the catalytic pocket. The DNA is distorted at the hemimethylated CpG step, with side chains from catalytic and recognition loops inserting through both grooves to fill an intercalation-type cavity associated with a dual base flip-out on partner strands. Structural and biochemical data establish how a combination of active and autoinhibitory mechanisms ensures the high fidelity of DNMT1-mediated maintenance DNA methylation.

PubMed: 22323818
DOI: 10.1126/science.1214453

Experimental method

X-RAY DIFFRACTION (2.6 Å)