The molecular forces shaping enzyme function and evolution : from hydrogen bonds to enzyme temperature adaptation
Abstract/Contents
- Abstract
- For billions of years, organisms and their enzymes have been evolving and adapting in response to selection pressures and opportunities presented by their environments. The mechanisms that underly enzyme adaptation are fundamental to our understanding of how enzymes work and the process of molecular evolution. Enzyme adaptation occurs through changes in the molecular interactions that specify enzyme structure and function. In particular, hydrogen bonds are central to how enzymes have evolved and are ubiquitous in enzyme structures, where they are often found in extended networks. Given the ubiquity and importance of hydrogen bonds, this dissertation seeks to understand the physical principles that govern hydrogen bond structure and energetics and their contribution to enzyme function and adaptation. I first define the physical principles that determine hydrogen bond lengths and energies. I then investigate the extent that hydrogen bonds in networks are coupled, structurally an energetically, to one another, improving our understanding of hydrogen bonds and the local and collective structural dynamics that exist within proteins and providing quantitative benchmarks for the design of hydrogen bonds and their networks. Second, to address the interplay between hydrogen bonds and other molecular interactions and enzyme evolution, I investigated enzyme temperature adaptation, as temperature profoundly influences enzyme stabilities and activities, providing a direct link between an environmental selection pressure and enzyme function. Performing deep mechanistic and structural studies and broad phylogenetic and sequence analyses, I identify new molecular mechanisms of enzyme temperature adaptation, test and revise nearly all prior proposals for enzyme adaptation to increased temperature, provide evidence that enzymes frequently adapt to temperature at sites of low epistasis, favoring parallel adaptation. This work improves our understanding of the molecular and evolutionary mechanisms underly enzyme evolution and suggests design principles that can be applied to enzyme engineering.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Pinney, Margaux Marie |
|---|---|
| Degree supervisor | Herschlag, Daniel |
| Thesis advisor | Herschlag, Daniel |
| Thesis advisor | Fordyce, Polly |
| Thesis advisor | Krasnow, Mark, 1956- |
| Thesis advisor | Yeh, Ellen |
| Degree committee member | Fordyce, Polly |
| Degree committee member | Krasnow, Mark, 1956- |
| Degree committee member | Yeh, Ellen |
| Associated with | Stanford University, Department of Biochemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Margaux Pinney. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/sy008bn3924 |
Access conditions
- Copyright
- © 2021 by Margaux Marie Pinney
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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