Mechanistic & spectroscopic studies on O2-activation and reactivity by coupled binuclear copper enzymes
Abstract/Contents
- Abstract
- Coupled binuclear copper (CBC) enzymes constitute a major family of O2-activating metalloenzymes that catalyze a wide range of oxidation and oxygenation reactions. The most predominant member of this enzyme family, tyrosinase (Ty) in its dicopper(I) reduced form (deoxy-Ty) binds O2 to form a μ-η2:η2-peroxide dicopper(II) intermediate (oxy-Ty) that can monooxygenate para-substituted monophenols to catechols, which in its native function constitutes the initial step in melanin biosynthesis in a wide range of organisms, from soil bacteria to humans. The mechanism of this important monooxygenation reaction has not been fully understood, with its key reaction intermediates remaining elusive. This thesis presents advancements in defining the monophenol monooxygenation mechanism of Ty by (i) trapping and spectroscopically characterizing key reaction intermediates, (ii) investigating their reactivity by kinetic methods, and (iii) correlating experimental results to quantum-mechanics/molecular-mechanics (QM/MM) calculations. Analysis of our experimental and computational results provides a molecular-level definition of the reaction coordinate for the monophenol monooxygenation reaction of Ty. This mechanism is different from the general paradigm based on previous model complex studies and provides new insights into how Nature employs Cu2O2 active sites to perform enzymatic catalysis.
Description
| Alternative title | Mechanistic and spectroscopic studies on O2-activation and reactivity by coupled binuclear copper enzymes |
|---|---|
| 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 | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Kipouros, Ioannis |
|---|---|
| Degree supervisor | Solomon, Edward I |
| Thesis advisor | Solomon, Edward I |
| Thesis advisor | Cegelski, Lynette |
| Thesis advisor | Stack, T. (T. Daniel P.), 1959- |
| Degree committee member | Cegelski, Lynette |
| Degree committee member | Stack, T. (T. Daniel P.), 1959- |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ioannis Kipouros. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/pt171qq3058 |
Access conditions
- Copyright
- © 2022 by Ioannis Kipouros
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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