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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 …