Advisor | Offenbacher, Adam | |
Author | Musgrave, Amy | |
Date Accessioned | 2019-06-26T16:59:30Z | |
Date Available | 2021-05-01T08:02:02Z | |
Date Created | 2019-05 | |
Date of Issue | 2019-05-03 | |
xmlui.metadata.dc.date.submitted | May 2019 | |
Identifier (URI) | http://hdl.handle.net/10342/7385 | |
Description | The enzymatic activity of human 15-lipoxygenase-2 (15-LOX-2) has been implicated in human inflammatory diseases such as atherosclerotic cardiovascular disease and plays an important role in maintaining homeostasis. 15-LOX-2 is one of six human lipoxygenase enzyme that catalyzes the (per)oxidation of fatty acids to produce both pro- and anti-inflammatory cellular signaling molecules.1 Despite its importance, current anti-inflammatories available on the market do not target lipoxygenase derived inflammation. There are three types of regulation of 15-LOX-2 activity: small allosteric regulators, selective inhibitors, and protein-protein/protein-membrane interactions. The first of these types of regulation is the focus of this study. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) allows for structural analysis of the complex formed with small allosteric regulators and selective inhibitors of 15-LOX-2. Using HDX-MS, we have shown excellent coverage of the primary sequence of 15-LOX-2 with dynamic properties comparable to previous reports. Further, in the presence of oleyl sulfate, a small molecule effector, regions of the protein were resolved to show alterations in protein flexibility. This data provides a basis for 15-LOX-2 regulation. | |
Mimetype | application/pdf | |
Publisher | East Carolina University | |
Subject | lipoxygenase | |
Subject | allostery | |
Subject | hydrogen-deuterium exchange (HDX) | |
Subject | HDX-MS | |
Subject | 15-LOX-2 | |
Title | Elucidation of allosteric behavior and enzyme-effector complexes of human 15-lipoxygenase-2 through hydrogen-detuerium exchange mass spectrometry | |
Type | Honors Thesis | |
xmlui.metadata.dc.date.updated | 2019-06-14T13:23:47Z | |
Department | Chemistry | |
xmlui.metadata.dc.degree.name | BS | |
xmlui.metadata.dc.degree.level | Undergraduate | |
xmlui.metadata.dc.degree.discipline | Chemistry | |
xmlui.metadata.dc.degree.grantor | East Carolina University | |
xmlui.metadata.dc.degree.department | Chemistry | |
xmlui.metadata.dc.access.option | Restricted Campus Access Only | |
xmlui.metadata.dc.embargo.lift | 2021-05-01 | |
xmlui.metadata.dc.type.material | text | |