General Acid Base Chemistry
editSimilar 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 [1] [2] [3] [4] .
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 [5] . 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)[6].
References
edit- ^ Rajagopal, Ponni; Feigon, Juli (22 June 1989). "Triple-strand formation in the homopurine:homopyrimidine DNA oligonucleotides d(G-A)4 and d(T-C)4". Nature. 339 (6226): 637–640. doi:10.1038/339637a0. PMID 2733796. S2CID 4313895.
{{cite journal}}: CS1 maint: date and year (link) - ^ Sklenár̆, Vladmír; Felgon, Juli (28 June 1990). "Formation of a stable triplex from a single DNA strand". Nature. 345 (6278): 836–838. doi:10.1038/345836a0. PMID 2359461.
- ^ Connell, Gregory J.; Yarus, Michael (20 May 1994). "RNAs with dual specificity and dual RNAs with similar specificity". Science. 264 (5162): 1137–1141. doi:10.1126/science.7513905. PMID 7513905.
- ^ Legault, Pascale; Pardi, Arthur (1994). "In situ Probing of Adenine Protonation in RNA by 13C NMR". Journal of the American Chemical Society. 116 (18): 8390–8391. doi:10.1021/ja00097a066.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: date and year (link) - ^ Ferré-d'Amaré, Adrian R.; Zhou, Kaihong; Doudna, Jennifer A. (8 October 1998). "Crystal structure of a hepatitis delta virus ribozyme". Nature. 395 (6702): 567–574. doi:10.1038/26912. PMID 9783582. S2CID 4359811.
- ^ Nakano, Shu-Ichi; Proctor, David J.; Bevilacqua, Philip C. (2001). "Mechanistic Characterization of the HDV Genomic Ribozyme: Assessing the Catalytic and Structural Contributions of Divalent Metal Ions within a Multichannel Reaction Mechanism". Biochemistry. 40 (40): 12022–12038. doi:10.1021/bi011253n. PMID 11580278.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: date and year (link)