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As shown in the mechanism, 2 Histidines and water are needed. The neutral histidine activates the 2' 2’ hydroxyl to attack the phosphate. The positively charged histidine enables the other hydroxyl to be a good leaving group.  Are you wondering why exactly we use histidine? Well, in order for this mechanism to perform successfully, you need an amino acid that is neutral. A neutral characteristic allows it to function as an acid and a base. An amino acid with stronger or weaker acid/base quality is less effective in activating the hydroxyls. With a pka of 7 (pka describes molecule), Histidine is the perfect candidate for a RNA nuclease.

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