Date of Award

11-7-2015

Degree Type

Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

First Advisor

Mutus, Bulent

Keywords

Acetylation, Protein Disulfide Isomerase

Rights

CC BY-NC-ND 4.0

Abstract

Protein disulfide isomerase (PDI) is crucial in the redox of disulfide bonds, where it catalyzes reductase, oxidase, and isomerase activity. The active site motif for PDI is CXXC, which is found in the a and a’ domain. PDI is mainly localized to the endoplasmic reticulum, where it plays a key role in the folding of new proteins through proper disulfide formation. With new studies about the regulation of protein activity by lysine acetylation, our group wished investigate this post-translational modification on PDI. Flanking each active site motif of PDI is a lysine residue. These active site-flanking lysine residues were mutated individually and together to observe if any catalytic change occurred. Mutation of the lysine residue to glutamine, alanine, or glutamic acid resulted in a decrease in activity, indicating the importance of the lysine residue for optimal PDI activity. Acetylation of PDI was performed by acetic anhydride, where through mass spectrometry, PDI was observed to be partially acetylated. The catalytic efficiency of the acetylated wt-PDI was observed to decrease in comparison to un-acetylated PDI. Indicating that acetylation of PDI may be a possible regulator of PDI redox activity.

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