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• W3186452345 abstract "Conditional remodeling of enzyme catalysis is a formidable challenge in protein engineering. Herein, we have undertaken a unique active site engineering tactic to command catalytic outcomes. With ten–eleven translocation (TET) enzyme as a paradigm, we show that variants with an expanded active site significantly enhance multistep C–H oxidation in 5-methylcytosine (5mC), whereas a crowded cavity leads to a single-step catalytic apparatus. We further identify an evolutionarily conserved residue in the TET family with a remarkable catalysis-directing ability. The activating variant demonstrated its prowess to oxidize 5mC in chromosomal DNA for potentiating expression of genes including tumor suppressors." @default.
• W3186452345 created "2021-08-02" @default.
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• W3186452345 date "2021-07-29" @default.
• W3186452345 modified "2023-10-16" @default.
• W3186452345 title "Catalytic Space Engineering as a Strategy to Activate C–H Oxidation on 5-Methylcytosine in Mammalian Genome" @default.
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• W3186452345 doi "https://doi.org/10.1021/jacs.1c03815" @default.
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