Substrate specificity of protein tyrosine phosphatase-like myo-inositol phosphatases: PhyA in complex with Ins(1,2,4,5,6)P5, Ins(1,3,4,5)P4, and Ins(1,4,5)P3

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dc.contributor.authorBruder, Lisza M.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorMosimann, Steven C.
dc.date.accessioned2019-06-12T17:36:15Z
dc.date.available2019-06-12T17:36:15Z
dc.date.issued2018
dc.degree.levelPh.Den_US
dc.description.abstractIn order to understand the substrate specificity of protein tyrosine phosphatase-like myo-inositol phosphatases (PTPLPs), I have determined the structure of PhyA from Mitsuokella multacida (PhyAmm) and Selenomonas ruminantium (PhyAsr) in complex with multiple myo-inositol phosphates (IPs). These are the first atomic resolution structures of PTPLPs in complex with InsP5, InsP4, or InsP3 substrates, and represent four of the five known PTPLP:IP complex structures. Based on these structures, I have identified three structural features that determine the substrate specificity of PTPLPs. As part of this work, I demonstrate that the PhyAmm C-terminal repeat and PhyAsr bind substrates using conserved phosphoryl-binding sites. Further, I have determined the InsP6 hydrolysis pathways for several PTPLPs and present a novel IP specificity assay. With this assay, I identify that the two repeats of PhyAmm have divergent activities that clearly indicate a ’divide and conquer’ approach to maximize phosphoryl group removal from InsP6 and mixed IPs.en_US
dc.embargoYesen_US
dc.identifier.urihttps://hdl.handle.net/10133/5394
dc.language.isoen_USen_US
dc.proquest.subject0487en_US
dc.proquest.subject0410en_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.subjectInositol -- Researchen_US
dc.subjectInositol phosphates -- Researchen_US
dc.subjectMetabolites -- Researchen_US
dc.subjectEnzymes -- Researchen_US
dc.subjectDissertations, Academicen_US
dc.subjectmyo-inositol phosphatesen_US
dc.subjectphosphoryl-bindingen_US
dc.subjectphosphoryl group removalen_US
dc.subjectPhyAen_US
dc.subjectPTPLPsen_US
dc.subjectsubstrate specificityen_US
dc.titleSubstrate specificity of protein tyrosine phosphatase-like myo-inositol phosphatases: PhyA in complex with Ins(1,2,4,5,6)P5, Ins(1,3,4,5)P4, and Ins(1,4,5)P3en_US
dc.typeThesisen_US
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