Mapping the Chemical Space of the RNA Cleavage and Its Implications for Ribozyme Catalysis

0486054 - BFÚ 2018 RIV US eng J - Journal Article
Mlýnský, V. - Kührová, P. - Jurečka, P. - Šponer, Jiří - Otyepka, M. - Banáš, Pavel
Mapping the Chemical Space of the RNA Cleavage and Its Implications for Ribozyme Catalysis.
Journal of Physical Chemistry B. Roč. 121, č. 48 (2017), s. 10828-10840. ISSN 1520-6106. E-ISSN 1520-5207
R&D Projects: GA ČR GAP208/12/1878
Institutional support: RVO:68081707
Keywords : delta-virus ribozyme * self-cleaving ribozymes
OECD category: Physical chemistry
Impact factor: 3.146, year: 2017

Ribozymes utilize diverse catalytic strategies. We report systematic quantum chemical calculations mapping the catalytic space of RNA cleavage by comparing all chemically feasible reaction mechanisms of RNA self-cleavage, using appropriate model systems including those chemical groups that may directly participate in ribozyme catalysis. We calculated the kinetics of uncatalyzed cleavage reactions proceeding via both monoanionic and dianionic pathways, and explicitly probed effects of various groups acting as general bases (GBs) and/or general acids (GAs), or electrostatic transition state stabilizers. In total, we explored 115 different mechanisms. The dianionic scenarios are generally preferred to monoanionic scenarios, although they may compete with one-another under some conditions. Direct GA catalysis seems to exert the dominant catalytic effect, while GB catalysis electrostatic stabilization are less efficient. Our results indirectly suggest that the dominant part of the catalytic effect might be explained by the shift of the reaction mechanism from the mechanism of uncatalyzed cleavage to the mechanism occurring in ribozymes. This would contrast typical protein enzymes, primarily achieving catalysis by overall electrostatic effects in their catalytic center.
Permanent Link: http://hdl.handle.net/11104/0280942