Allosteric regulation and function of GTPases
Date
2019
Authors
Girodat, Dylan J.
University of Lethbridge. Faculty of Arts and Science
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Journal ISSN
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Publisher
Lethbridge, Alta. : University of Lethbridge, Department of Chemistry and Biochemistry
Abstract
Guanosine triphosphatases (GTPases) are some of the most vital and versatile molecular switches found in all domains of life. For proper functionality these enzymes require allosteric regulation mediated by ligand binding. This thesis highlights three key problems in allosteric regulation: equilibrium, transmission, and transition, investigating how GTPases address each problem. The free energy equilibrium upon nucleotide binding to Elongation Factor (EF)-Tu was investigated to describe how GTPases tackle the equilibrium problem of allostery. Additionally, the mechanism of how the ribosome allosterically regulates the GTPase activity of EF-Tu was investigated to describe how GTPases can solve the transmission problem of allostery. Lastly, the D2 dopamine receptor conformational ensemble revealed how the transition problem of allostery can be addressed in guanosine nucleotide exchange factors. Altogether this thesis provides a framework which can be used to study the three problems of allostery in any protein, highlighting strategies utilized by GTPases.
Description
Keywords
Guanosine triphosphatase -- Research , Allosteric regulation -- Research , Enzymes -- Regulation -- Research , allosteric regulation , allostery , EF-Tu , GTPases , guanosine triphosphatases , molecular switches , Dissertations, Academic