Allosteric regulation and function of GTPases

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dc.contributor.authorGirodat, Dylan J.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorWieden, Hans-Joachim
dc.date.accessioned2019-08-14T15:33:44Z
dc.date.available2019-08-14T15:33:44Z
dc.date.issued2019
dc.degree.levelPh.Den_US
dc.description.abstractGuanosine 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.en_US
dc.description.sponsorshipAlberta Innovates (Strategic Chairs Program [SC60-T2] Natural Sciences and Engineering Research Discovery Grant [RGPIN-2016-05199] Alberta Innovates Technology Futures Graduate Student Scholarshipen_US
dc.identifier.urihttps://hdl.handle.net/10133/5493
dc.language.isoen_USen_US
dc.proquest.subject0786en_US
dc.proquest.subject0487en_US
dc.proquest.subject0307en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Department of Chemistry and Biochemistryen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectGuanosine triphosphatase -- Researchen_US
dc.subjectAllosteric regulation -- Researchen_US
dc.subjectEnzymes -- Regulation -- Researchen_US
dc.subjectallosteric regulationen_US
dc.subjectallosteryen_US
dc.subjectEF-Tuen_US
dc.subjectGTPasesen_US
dc.subjectguanosine triphosphatasesen_US
dc.subjectmolecular switchesen_US
dc.subjectDissertations, Academicen_US
dc.titleAllosteric regulation and function of GTPasesen_US
dc.typeThesisen_US
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