Date of Award
Fall 12-17-2019
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Donald Hamelberg
Second Advisor
Gregory Poon
Third Advisor
Shahab Shamsi
Abstract
Understanding how conformational dynamics play a role in metabolic regulation is an important objective in various biological disciplines. Using Molecular Dynamics (MD) simulations, we attempt to elucidate the dynamics involved in regulating two glycolytic enzymes: human liver pyruvate kinase (hL-PYK) and human enolase. Despite being metabolically coupled, both enzymes are regulated quite differently: hL-PYK can undergo allosteric modulation, while enolase is competitively inhibited. In the hL-PYK study, we discern a mechanism of allostery induced by the allosteric activator fructose-1,6-bisphosphate, and the inhibitor alanine. In the case of enolase, previous studies have attempted to make isoform-specific inhibitors of the enzyme; to further explore this objective, we compare the dynamics of two conserved isozymes, enolase 1 and 2, through MD simulations. As a proof of concept, we find compounds that discriminate between the two homologues by performing ensemble virtual screening on MD derived free enolase structures.
Recommended Citation
Shouaib, Abdullah, "Exploring the Dynamics of Glycolytic Regulation Through Two Enzymes: Human Enolase and Liver Pyruvate Kinase." Thesis, Georgia State University, 2019.
https://scholarworks.gsu.edu/chemistry_theses/134
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