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General Acid Base Chemistry
Similar to the hairpin ribozyme, the HDV ribosome has reactions that is characterized by acid-base catalysis. The functional groups within the protein has neutral pH’s has close pH values that allows it to interchange between the acid and base phase. This behavior shows that the HDV ribozyme must have some form of functional groups that has neutral like pH around 6 to 7. Within RNA, typical pKa values for the free nucleosides are around 3.5 to 4.2, a lower pKa acidic value that would unlikely become basic. However, due to the shifted pKa values that causes the acid-base catalysis, there is a likelihood that it may be caused form the structural environment within the nucleoside.

Within the HDV Ribozyme, there is a network of hydrogen bonds to the cytosine that is able to stabilize the protonated form of the cytosine. It will allow the donation and acceptance of the proton at some during the catalysis. In a set of experiments, a point mutations was done to the critical cytosine. Afterwards there was a drop activity and was partially restored when imidazole was added.

With support data, the current model of cytosine acting as a general acid within the reaction to donate a proton to the 5’-bridging oxygen (See figure). There is also a metal ion that coordinates near the ribozyme active site to abstract a proton from the 2’-hydroxyl nucleophile (37).