The zinc metalloprotease neprilysin (NEP) has been shown to degrade small bioactive peptides. Crystal structures of seven NEP-inhibitor complexes and biochemical characterization of NEP activity have highlighted amino acid interactions that are crucial to ligand binding. Studies also indicate that NEP is one of a select group of metalloenzymes that degrade the amyloid-beta peptide (Aß) in vivo and in situ. Accumulation of neurotoxic Aß aggregates in the brain appears to be a causative agent in the pathophysiology of Alzheimer's Disease (AD). For this reason the enzymatic degradation of Aß has been studied extensively, but little is known about specific binding interactions underlying NEP degradation of Aß. Using known crystal structures of NEP, we have conducted comparative computational studies of ligand binding that predict NEP residues Arg 102 and 110 form binding interactions specific to Aß. These interactions may provide insight for using NEP degradation of Aß in AD therapy. / Bayer School of Natural and Environmental Sciences; / Chemistry and Biochemistry; / MS; / Thesis;
| Identifer | oai:union.ndltd.org:DUQUESNE/oai:digital.library.duq.edu:etd/162309 |
| Date | 15 October 2013 |
| Creators | Pope, Darrick Earle |
| Contributors | Michael Cascio, Jeffry Madura, Rita Mihailescu |
| Source Sets | Duquesne University |
| Detected Language | English |
| Rights | Six month embargo: no access to PDF file until release date by author request.; |
Page generated in 0.0023 seconds