Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Biology
Investigation Of The Mechanisms Governing Carrier Domain Translocation In S. Aureus Pyruvate Carboxylase, Joshua Hakala
Investigation Of The Mechanisms Governing Carrier Domain Translocation In S. Aureus Pyruvate Carboxylase, Joshua Hakala
Dissertations (1934 -)
A central debate in protein biochemistry focuses on the mechanism by which ligands contribute to conformational changes in proteins. Two primary hypotheses describe this process: the induced-fit hypothesis and the conformational ensembles hypothesis. In contrast to the induced-fit hypothesis, the conformational ensembles hypothesis states that the protein pre-exists in multiple conformational states, with ligand binding shifting the equilibrium towards a preferred conformation. The contribution of ligand binding to large-scale conformational changes is particularly relevant to multi-domain “swinging-arm” enzymes, for which pyruvate carboxylase (PC) serves as a well characterized paradigm system. PC catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate. The …
The Discovery And Characterization Of Small Molecule Inhibitors Of Pyruvate Carboxylase, Brittney Wyatt
The Discovery And Characterization Of Small Molecule Inhibitors Of Pyruvate Carboxylase, Brittney Wyatt
Dissertations (1934 -)
Pyruvate carboxylase is a metabolically important enzyme that has been implicated in a wide range of diseases and infections such as cancer, diabetes and listeriosis. Despite the importance of pyruvate carboxylase in these diseases and infections, there are no selective and potent small molecule effectors available to study pyruvate carboxylase both in vitro and in vivo. Effective small molecule effectors of pyruvate carboxylase will expand the biochemical toolkit to facilitate the investigation of the structure, regulation and specific cellular role of pyruvate carboxylase. To discover small molecule effectors of pyruvate carboxylase, a novel fixed time assay was developed. The assay …