Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation

Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation

Bibliographic Details
Main Author: Kellerman, Daniel
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2016
Subjects:
Biochemistry
kinetic isotope effects
HDV ribozyme
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1449150064
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case14491500642021-08-03T06:34:22Z Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation Kellerman, Daniel Biochemistry kinetic isotope effects HDV ribozyme 18O kinetic isotope effects for RNA 2’-O-transphosphorylation reactions have been determined, characterizing the bonding in the transition states for RNA cleavage by specific base and by specific acid in solution. These results provide demonstrate a late, product-like transition state for the specific base reaction and provide evidence for equilibrium deprotonation of the 2’O nucleophile. Additionally, they further confirm a step-wise mechanism involving a protonated, phosphorane intermediate for the specific acid catalyzed reaction. Finally, series of structure function studies using internal competition as an analytical tool examine the role of the 2’O nucleophile during the RNA 2’-O-transphosphorylation reaction catalyzed by the HDV ribozyme. These results directly test a hypothetical pairing interaction within the catalytic core of the ribozyme and provided the first atomic level detail on which functional groups contribute to positioning the 2’O nucleophile. 2016-01-27 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1449150064 http://rave.ohiolink.edu/etdc/view?acc_num=case1449150064 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Biochemistry
kinetic isotope effects
HDV ribozyme
spellingShingle Biochemistry
kinetic isotope effects
HDV ribozyme
Kellerman, Daniel
Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation
author Kellerman, Daniel
author_facet Kellerman, Daniel
author_sort Kellerman, Daniel
title Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation
title_short Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation
title_full Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation
title_fullStr Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation
title_full_unstemmed Application of Internal Competition Kinetics to Probe the Catalytic Strategies of RNA 2’-O-transphosphorylation
title_sort application of internal competition kinetics to probe the catalytic strategies of rna 2’-o-transphosphorylation
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2016
url http://rave.ohiolink.edu/etdc/view?acc_num=case1449150064
work_keys_str_mv AT kellermandaniel applicationofinternalcompetitionkineticstoprobethecatalyticstrategiesofrna2otransphosphorylation
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