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CpG methyltransferase M.SssI is a prokaryotic enzyme originally isolated from Spiroplasma sp. strain MQ1 that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to the C5 position of cytosine within CpG dinucleotides (UniProt P14755). It is functionally analogous to mammalian DNA methyltransferase 1 (DNMT1) and is frequently used as a surrogate model in biochemical assays to screen for and characterize epigenetic drugs (PMID: 15615711). The enzyme is a critical tool in research for generating methylated DNA templates and studying the impact of DNA methylation on gene expression and chromatin structure (NEB M0226). While M.SssI itself is not a human therapeutic target, it is a primary target for inhibitors like decitabine and azacitidine in experimental settings aimed at treating hematological malignancies. Its ability to methylate all CpG sites makes it an essential reference for evaluating the potency of demethylating agents in oncology drug development. Consequently, it plays a significant role in the discovery of therapies targeting aberrant DNA methylation patterns in diseases such as cancer.
Inhibition of DNA methyltransferase activity via covalent trapping on aza-nucleoside-substituted DNA or competitive inhibition of the S-adenosyl-L-methionine binding site.
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