Date of Graduation

12-2020

Document Type

Thesis

Degree Name

Master of Science in Chemistry (MS)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Wesley Stites

Committee Member

Josh Sakon

Second Committee Member

Jackson Lay, Jr.

Third Committee Member

Chenguang Fan

Keywords

Cell signaling processes, Conservation, Disease Progression, Methionine, Methionine Sulfoxide, Oxidation, Proteins, Residues

Abstract

In previous work from this laboratory, methionine containing peptides from the human urinary proteome were examined by mass spectrometry for the degree of methionine oxidation to the sulfoxide form. While this demonstrated that many of the methionines detected were capable of being oxidized, the question of whether these methionines are important in the structure and/or function of the parent proteins came about. In some proteins, methionine oxidation has been linked to conformational changes and alteration of function and thus can serve as a mechanism for reversible regulation of activity. It is hypothesized that methionines which might serve a regulatory purpose when cycled between the thioether and sulfoxide form will be conserved throughout many species. A list of species whose genomes have been sequenced was designed to span a wide distance across the phylogenetic tree, so that conservation of specific methionines could be analyzed. Some methionines that were susceptible to oxidation were found to be much more conserved than other methionines and also more conserved than their surrounding residues. It is hypothesized that upon further study, these methionines will prove to be more important to the structure and/or function of their respective proteins than the other methionines that were less conserved than their surroundings or those with a low overall conservation. Focusing future work to examine the impact upon protein structure and function of oxidation and reduction of this group of conserved methionines would seem more likely to be fruitful than a broad examination of the redox effect of all methionines.

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