The purification and characterization of USP30
| Author(s) | Cargill, Jason | |
| Date Accessioned | 2018-03-26T11:44:11Z | |
| Date Available | 2018-03-26T11:44:11Z | |
| Publication Date | 2017 | |
| SWORD Update | 2017-11-10T14:20:23Z | |
| Abstract | Parkinson is the second most prevalent neurological disorder behind Alzheimer’s, affecting over 1 million Americans a year. The disintegration of dopamine producing neural cells in the substania nigra is the apparent cause of Parkinson. However, the underlying mechanism of impairment is still not well understood. Currently, the most common medications prescribed to Parkinson’s patients only treat the symptoms of dopamine loss, either by mimicking dopamine or by altering dopamine levels. These medications do nothing to regress the disease itself. A line of research that would lead to a treatment of the underlying mechanism is much needed. Mounting research points in the direction of mitochondria malfunction as a key factor in the development of Parkinson’s. The ubiquitin specific protease USP30 plays a significant role in the management of healthy mitochondria, by acting to regulate the destruction of damaged mitochondrion. A knockdown of the USP30 gene has been shown to alleviate Parkinson’s symptoms in flies with parkin mutation. Other promising studies suggest that the USP30 enzyme would be a good target for potential inhibitor studies. However few studies have been performed on the isolated protein itself. In this study, we attempt to close that gap by developing a method to purify large quantities of the enzyme to be used in inhibitor studies and for x ray crystallography. Further evidence for the potential of inhibitor studies is the unique catalytic triad of USP30 (Cys-Asp-Ser). To gain a better understanding of the active site, which could be exploited when developing an inhibitor, we prepared and characterized individual mutants of each of the three amino acids. | en_US |
| Advisor | Zhuang, Zhihao | |
| Degree | M.S. | |
| Department | University of Delaware, Department of Chemistry and Biochemistry | |
| Unique Identifier | 1029540141 | |
| URL | http://udspace.udel.edu/handle/19716/23113 | |
| Language | en | |
| Publisher | University of Delaware | en_US |
| URI | https://search.proquest.com/docview/2002369221?accountid=10457 | |
| Keywords | Pure sciences | en_US |
| Title | The purification and characterization of USP30 | en_US |
| Type | Thesis | en_US |