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Impact of Nucleic Acid Backbone Composition On Tet2
The TET2 enzyme mediates the stepwise conversion of 5-methylcytosine (5mC) to 5-carboxylcytosine (5caC). Previously, our experimental and computational work identified structural differences between both single-stranded (ss) and double-stranded (ds) DNA and RNA, as well as mixed DNA-RNA substrates (Biochemistry 58 (2019) 411). TET2 was found to selectively favor double-stranded substrates over single-stranded substrates, and all-DNA substrates over DNA-RNA or all-RNA substrates. Changes to the substrate affected the active site configuration. In this contribution, we will present molecular dynamics simulations performed on TET2 with a variety of backbone compositions. These simulations investigate how a residueu2019s identity (e.g., oxidation product or DNA vs. RNA) in the substrate-, complement-, or both substrate and complement strands impact the structure and dynamics of TET2. This poster will discuss how the composition of both the substrate and complement impact 5mC oxidation.
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