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Development of carbon-13 nuclear mag...

University of Michigan.

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Development of carbon-13 nuclear magnetic resonance methods for studying the structural dynamics of nucleic acids in solution .

Record Type:	Electronic resources : Monograph/item
Title/Author:	Development of carbon-13 nuclear magnetic resonance methods for studying the structural dynamics of nucleic acids in solution ./
Author:	Hansen, Alexandar Louis.
Description:	151 p.
Notes:	Adviser: Hashim M. Al-Hashimi.
Contained By:	Dissertation Abstracts International70-04B.
Subject:	Biophysics, General. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3354162
ISBN:	9781109115246

Development of carbon-13 nuclear magnetic resonance methods for studying the structural dynamics of nucleic acids in solution .
Hansen, Alexandar Louis.

Development of carbon-13 nuclear magnetic resonance methods for studying the structural dynamics of nucleic acids in solution . - 151 p.

Adviser: Hashim M. Al-Hashimi.

Thesis (Ph.D.)--University of Michigan, 2009.

An understanding of both structure and dynamics is essential to the full characterization of any biomolecule, but is especially relevant with respect to RNA for which dynamics is used in myriad ways to achieve functional complexity that would otherwise be inaccessible based on its rigid framework composed of only four chemically similar nucleotides. Due to experimental difficulties in resolving the plethora of motional modes that exist in RNA, their dynamical properties remain poorly understood. Solution nuclear magnetic resonance (NMR) is one of the most powerful tools for the characterization of structural dynamics, as it provides atomic level detail on a variety of timescales, from picoseconds to seconds. Spin relaxation measurements can in principle provide information at sub-nanosecond timescales, providing that internal motions are not correlated to overall molecular tumbling. Residual dipolar couplings and residual chemical shift anisotropies (RCSAs) report on the average global RNA structure and provide insight into sub-millisecond motions. Finally, chemical exchange measurements can provide quantitative kinetic information on the micro-to-millisecond timescale. Unfortunately, many of the techniques commonly used for studies of RNA are limited to nitrogen resonances, which are not frequently observable in functionally relevant, non-canonical regions of RNA. In addition, target RNAs are relatively small, typically less than 30 nucleotides or 10,000 molecular weight. In this thesis, I develop the much needed NMR methods which can target the carbon nuclei of RNA and in systems up to 150 nucleotides. A combination of new spin relaxation, RCSA, and chemical exchange techniques are developed to probe site specific motions over the picosecond to millisecond time regime and provide important insight into some of the fundamental properties of RNA. Spin relaxation revealed a surprisingly complex dynamical landscape for the relatively simple transactivation response element from HIV-1 RNA where intriguing entropy compensation occurs upon ligand binding in the bulge region, with order parameters of 0.2--0.3, as global domain motions are suppressed. New, selective R1ϱ, dispersion experiments detected previously unobservable chemical exchange in functionally important regions of the bacterial ribosomal A-site RNA, with a timescale of 320 mus, and the modified base in a 1,N6-ethenoadenine - damaged DNA.

ISBN: 9781109115246Subjects--Topical Terms:

1019105
Biophysics, General.

Development of carbon-13 nuclear magnetic resonance methods for studying the structural dynamics of nucleic acids in solution .
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100 1 $a Hansen, Alexandar Louis. $3 1043619
245 1 0 $a Development of carbon-13 nuclear magnetic resonance methods for studying the structural dynamics of nucleic acids in solution .
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502 $a Thesis (Ph.D.)--University of Michigan, 2009.
520 $a An understanding of both structure and dynamics is essential to the full characterization of any biomolecule, but is especially relevant with respect to RNA for which dynamics is used in myriad ways to achieve functional complexity that would otherwise be inaccessible based on its rigid framework composed of only four chemically similar nucleotides. Due to experimental difficulties in resolving the plethora of motional modes that exist in RNA, their dynamical properties remain poorly understood. Solution nuclear magnetic resonance (NMR) is one of the most powerful tools for the characterization of structural dynamics, as it provides atomic level detail on a variety of timescales, from picoseconds to seconds. Spin relaxation measurements can in principle provide information at sub-nanosecond timescales, providing that internal motions are not correlated to overall molecular tumbling. Residual dipolar couplings and residual chemical shift anisotropies (RCSAs) report on the average global RNA structure and provide insight into sub-millisecond motions. Finally, chemical exchange measurements can provide quantitative kinetic information on the micro-to-millisecond timescale. Unfortunately, many of the techniques commonly used for studies of RNA are limited to nitrogen resonances, which are not frequently observable in functionally relevant, non-canonical regions of RNA. In addition, target RNAs are relatively small, typically less than 30 nucleotides or 10,000 molecular weight. In this thesis, I develop the much needed NMR methods which can target the carbon nuclei of RNA and in systems up to 150 nucleotides. A combination of new spin relaxation, RCSA, and chemical exchange techniques are developed to probe site specific motions over the picosecond to millisecond time regime and provide important insight into some of the fundamental properties of RNA. Spin relaxation revealed a surprisingly complex dynamical landscape for the relatively simple transactivation response element from HIV-1 RNA where intriguing entropy compensation occurs upon ligand binding in the bulge region, with order parameters of 0.2--0.3, as global domain motions are suppressed. New, selective R1ϱ, dispersion experiments detected previously unobservable chemical exchange in functionally important regions of the bacterial ribosomal A-site RNA, with a timescale of 320 mus, and the modified base in a 1,N6-ethenoadenine - damaged DNA.
590 $a School code: 0127.
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792 $a 2009
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