Structure and substrate specificity of myo-inositol phosphatases at atomic resolution

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dc.contributor.authorBruder, Lisza M.
dc.contributor.supervisorMosimann, Steven C.
dc.date.accessioned2014-08-29T16:18:57Z
dc.date.available2014-08-29T16:18:57Z
dc.date.issued2013
dc.degree.levelMastersen_US
dc.descriptionx, 73 leaves : ill. (chiefly col.) ; 29 cmen_US
dc.description.abstractProtein tyrosine phosphatase-like myo-inositol phosphatases (PTPLPs) follow an ordered, sequential dephosphorylation pathway that utilizes the abundant myo-inositol- 1,2,3,4,5,6-hexakisphosphate (InsP6) to produce less-phosphorylated myo-inositol phosphates (IPs) containing between one and five phosphoryl groups. To understand PTPLP substrate specificity, I present multiple complex structures of Phytase A from Selenomonas ruminantium (PhyAsr) and Mitsuokella multacida (PhyAmm; a tandem repeat) with various IPs. From these structures I demonstrated that binding of IPs by these enzymes is consistent with a 'lock-and-key' binding mechanism, determined binding differences between InsP6 and less-phosphorylated IPs, and revised the existing PTPLP substrate specificity model. As part of this work, I have produced the first PhyAmm complex structures and demonstrated that the PhyAmm C-terminal repeat binds substrates using identical phosphoryl binding sites as PhyAsr. Further, I have provided evidence that differential substrate binding in the PhyAmm N- and C-terminal repeats is due to electrostatic differences and a loop insertion causing steric clashes.en_US
dc.identifier.urihttps://hdl.handle.net/10133/3492
dc.language.isoen_CAen_US
dc.proquestyesNoen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. 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.subjectDissertations, Academicen_US
dc.titleStructure and substrate specificity of myo-inositol phosphatases at atomic resolutionen_US
dc.typeThesisen_US
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