7CY8

Crystal Structure of CMD1 in complex with 5mC-DNA and vitamin C

7CY8 の概要

• エントリーDOI: 10.2210/pdb7cy8/pdb
• 分子名称: Maltodextrin-binding protein,5-methylcytosine-modifying enzyme 1, DNA (5'-D(P*(5CM)P*GP*CP*GP*CP*GP*GP*GP*A)-3'), ASCORBIC ACID, ... (7 entities in total)
• 機能のキーワード: tet, vitamin c, dioxygenase, 5gmc, dna modification, 2-oxoglutarate, transferase
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 107953.26

構造登録者

Li, W.,Zhang, T.,Sun, M.,Ding, J. (登録日: 2020-09-03, 公開日: 2020-12-30, 最終更新日: 2023-11-29)

主引用文献

Li, W.,Zhang, T.,Sun, M.,Shi, Y.,Zhang, X.J.,Xu, G.L.,Ding, J.
Molecular mechanism for vitamin C-derived C 5 -glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1.
Nat Commun, 12:744-744, 2021

PubMed Abstract: C-glyceryl-methylcytosine (5gmC) is a novel DNA modification catalyzed by algal TET homologue CMD1 using vitamin C (VC) as co-substrate. Here, we report the structures of CMD1 in apo form and in complexes with VC or/and dsDNA. CMD1 exhibits comparable binding affinities for DNAs of different lengths, structures, and 5mC levels, and displays a moderate substrate preference for 5mCpG-containing DNA. CMD1 adopts the typical DSBH fold of Fe/2-OG-dependent dioxygenases. The lactone form of VC binds to the active site and mono-coordinates the Fe in a manner different from 2-OG. The dsDNA binds to a positively charged cleft of CMD1 and the 5mC/C is inserted into the active site and recognized by CMD1 in a similar manner as the TET proteins. The functions of key residues are validated by mutagenesis and activity assay. Our structural and biochemical data together reveal the molecular mechanism for the VC-derived 5gmC DNA modification by CMD1.

PubMed: 33531488
DOI: 10.1038/s41467-021-21061-2

実験手法

X-RAY DIFFRACTION (2.4 Å)