Molecular mechanism for vitamin C-derived C⁵-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1.

ABSTRACT: C⁵-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 Fe²⁺/2-OG-dependent dioxygenases. The lactone form of VC binds to the active site and mono-coordinates the Fe²⁺ 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 k

SUBMITTER: Li W 

PROVIDER: S-EPMC7854593 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature