3EPZ

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

3EPZ の概要

• エントリーDOI: 10.2210/pdb3epz/pdb
• 分子名称: DNA (cytosine-5)-methyltransferase 1, ZINC ION, beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: winged helix domain, sh3-like barrel, cell cycle, metal binding, dna binding, dna replication, transcriptional silencing, chromatin, phosphorylation, transcription, transcription regulation, transferase, epigenetics zinc, zinc-finger, methyltransferase, nucleus, phosphoprotein, repressor, s-adenosyl-l-methionine, structural genomics, structural genomics consortium, sgc
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61256.43

構造登録者

Walker, J.R.,Avvakumov, G.V.,Xue, S.,Li, Y.,Bountra, C.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (登録日: 2008-09-30, 公開日: 2008-11-25, 最終更新日: 2024-10-30)

主引用文献

Syeda, F.,Fagan, R.L.,Wean, M.,Avvakumov, G.V.,Walker, J.R.,Xue, S.,Dhe-Paganon, S.,Brenner, C.
The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of Dnmt1.
J.Biol.Chem., 286:15344-15351, 2011

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.

PubMed: 21389349
DOI: 10.1074/jbc.M110.209882

実験手法

X-RAY DIFFRACTION (2.31 Å)