3AV6

Crystal structure of mouse DNA methyltransferase 1 with AdoMet

3AV6 の概要

• エントリーDOI: 10.2210/pdb3av6/pdb
• 分子名称: DNA (cytosine-5)-methyltransferase 1, ZINC ION, S-ADENOSYLMETHIONINE (3 entities in total)
• 機能のキーワード: cxxc-type zinc finger/c5-methyltransferase family, methylates cpg residues, preferentially methylates hemimethylated dna, dna binding, hemi-methylation, nucleus, transferase
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 151456.54

構造登録者

Takeshita, K.,Suetake, I.,Yamashita, E.,Suga, M.,Narita, H.,Nakagawa, A.,Tajima, S. (登録日: 2011-02-22, 公開日: 2011-05-04, 最終更新日: 2023-11-01)

主引用文献

Takeshita, K.,Suetake, I.,Yamashita, E.,Suga, M.,Narita, H.,Nakagawa, A.,Tajima, S.
Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).
Proc.Natl.Acad.Sci.USA, 108:9055-9059, 2011

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.

PubMed: 21518897
DOI: 10.1073/pnas.1019629108

実験手法

X-RAY DIFFRACTION (3.09 Å)