Mechanochemical coupling and structural dynamics in DNA gyrase
Abstract/Contents
- Abstract
- DNA gyrase is a molecular motor that directionally introduces negative supercoils into DNA, serving a function that is critical to most bacterial life. This thesis addresses the question of how gyrase transduces chemical energy stored in ATP into mechanical energy stored in supercoiled DNA. I have investigated how substeps in the ATPase cycle -- ATP binding, hydrolysis and product release -- coordinate structural transitions of the nucleoprotein complex during the course of the supercoiling reaction. Using single-molecule real-time tracking of DNA compaction and rotation, I have characterized the geometry and interconversion dynamics of DNA configurations under different nucleotide conditions. A critical step in the reaction cycle of DNA gyrase involves the formation and manipulation of a chiral wrap in the path of DNA on a scale of ~ 150 base pairs. I show that chiral wrapping is a multistep process that dominates the overall kinetics and is modulated by ATP. My results identify new roles for ATP binding, hydrolysis and product release, and show that nucleotide states in gyrase cannot be uniquely identified with structural intermediates. The work reveals a sophisticated molecular motor in which a conformational landscape of loosely coupled transitions funnels the enzyme toward productive energy transduction.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2013 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Basu, Aakash | |
|---|---|---|
| Associated with | Stanford University, Department of Applied Physics. | |
| Primary advisor | Bryant, Zev David | |
| Primary advisor | Fisher, Daniel S | |
| Thesis advisor | Bryant, Zev David | |
| Thesis advisor | Fisher, Daniel S | |
| Thesis advisor | Puglisi, Joseph D | |
| Advisor | Puglisi, Joseph D |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Aakash Basu. |
|---|---|
| Note | Submitted to the Department of Applied Physics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2013. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2013 by Aakash Basu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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