{"id":{"repo_id":"lethbridge","oai_identifier":"oai:opus.uleth.ca:10133/5394"},"canonical_url":"https://search.dev.ndltd.org/etd/lethbridge/oai:opus.uleth.ca:10133/5394","repository":{"repo_id":"lethbridge","name":"University of Lethbridge","base_url":"https://opus.uleth.ca/server/oai/request"},"display":{"title":"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","abstract":"In 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.","abstract_html":"In 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.","abstract_has_math":false,"creators":["Bruder, Lisza M.","University of Lethbridge. Faculty of Arts and Science"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018","date_published":"2018","updated_at":"2026-07-27T20:02:29Z","subjects":["Inositol -- Research","Inositol phosphates -- Research","Metabolites -- Research","Enzymes -- Research","Dissertations, Academic","myo-inositol phosphates","phosphoryl-binding","phosphoryl group removal","PhyA","PTPLPs","substrate specificity"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/5394"],"render_values":[{"text":"hdl:10133/5394","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2018"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Inositol -- Research","Inositol phosphates -- Research","Metabolites -- Research","Enzymes -- Research","Dissertations, Academic","myo-inositol phosphates","phosphoryl-binding","phosphoryl group removal","PhyA","PTPLPs","substrate specificity"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/5394"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["In 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."]},{"key":"dc:title","label":"Title","values":["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"]}]}],"canonical_facts":{"dc:date.issued":["2018"],"dc:description.other":["In 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."],"dc:identifier":["hdl:10133/5394"],"dc:subject":["Inositol -- Research","Inositol phosphates -- Research","Metabolites -- Research","Enzymes -- Research","Dissertations, Academic","myo-inositol phosphates","phosphoryl-binding","phosphoryl group removal","PhyA","PTPLPs","substrate specificity"],"dc:title":["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"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T20:02:29Z"}