Evaluation of the variation of ketosteroid isomerase from enzyme energetics to evolution
Abstract/Contents
- Abstract
- Enzymes are exceptional catalysts that facilitate chemistry on the timescale of life. In this thesis, I discuss experimental and conceptual advances in understanding enzyme traits from an energetic and evolutionary perspective. First, I test the hypothesis that enzymes adapt to cold through rate enhancement. I do not find evidence of cold adaptation through rate enhancement broadly across the literature or in the model enzyme ketosteroid isomerase (KSI), despite prior expectation and evidence for rate-based temperature adaptation. I further evaluate energetic independence and additivity in the active site of KSI where I develop a model to account for observed rate variation based on naturally occurring active site changes in twenty KSI variants. I also review techniques to measure protein stability spanning large-scale and small-scale measurements. Integrating measurement approaches at different scales will be critical to develop and test physical models of enzyme traits such as stability and rate. Overall, this work enhances our understanding of enzyme energetics spanning rate and protein folding from an evolutionary perspective. I close this thesis with a perspective on principles of rubric development for use in graduate admissions. As the development of fair and effective criteria for graduate admissions presents a pressing challenge, I seek to normalize changing policy that does not serve our values in our places of research and I address the responsibility that we have as scientists to alleviate inequities and injustices present in our society.
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 | Stark, Catherine DuBrule |
|---|---|
| Degree supervisor | Herschlag, Daniel |
| Thesis advisor | Herschlag, Daniel |
| Thesis advisor | Harbury, Pehr |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Degree committee member | Harbury, Pehr |
| Degree committee member | Khosla, Chaitan, 1964- |
| Associated with | Stanford University, Department of Biochemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Catherine DuBrule Stark. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/nj753hw9922 |
Access conditions
- Copyright
- © 2021 by Catherine DuBrule Stark
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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