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Date of Award
Restricted Thesis: Campus only access
Bachelor of Science
Dr. Ellis Bell
The oxidoreductase glutamate dehydrogenase (GDH) has evolved from exhibiting virtually no allosteric regulation in prokaryotes to being regulated by numerous allosteric ligands in mammals. We report creating homology models of GDH from seven organisms that have evolved at different times, in order to study the evolution of the allosteric regulation of the enzyme and to see whether we can relate evolutionary trajectories to enzymatic structure. Overall, the most prominent variations in structure between the homology models are observed at the N-terminus and at the antenna domain. The binding sites for the major allosteric inhibitor GTP and the major allosteric activator ADP in the homology models were compared to the corresponding binding sites in bovine glutamate dehydrogenase. The fruit fly Drosophila melanogaster is the only enzyme that has a GTP binding site, while GDH from fruit fly and several unicellular eukaryotes possess an ADP binding site. A putative ADP binding site was found in tobacco GDH. Reconciliation with an organismal phylogeny suggests that GTP regulation arose in Metazoa, while ADP regulation and the antenna domain arose concurrently in the eukaryotic lineage and were lost twice.
Lekova, Virzhiniya, "Homology modeling provides insight into the evolution of allostery of glutamate deydrogenase" (2010). Honors Theses. 142.