7cy6
From Proteopedia
Crystal Structure of CMD1 in complex with 5mC-DNA
Structural highlights
FunctionMALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.CMD1_CHLRE Dioxygenase that catalyzes DNA modification by mediating the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-glyceryl-methylcytosine (5gmC) (PubMed:31043749, PubMed:33531488). Catalyzes the conjugation of a glyceryl moiety from L-ascorbate (vitamin C) to the methyl group of 5mC through a carbon-carbon bond (PubMed:31043749, PubMed:33531488). 5gmC DNA modification may be required during photosynthesis as an epigenetic mark that couteracts DNA methylation (PubMed:31043749).[1] [2] Publication Abstract from PubMedC(5)-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+)/2-OG-dependent dioxygenases. The lactone form of VC binds to the active site and mono-coordinates the Fe(2+) 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. Molecular mechanism for vitamin C-derived C(5)-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1.,Li W, Zhang T, Sun M, Shi Y, Zhang XJ, Xu GL, Ding J Nat Commun. 2021 Feb 2;12(1):744. doi: 10.1038/s41467-021-21061-2. PMID:33531488[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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