{"id":{"repo_id":"lethbridge","oai_identifier":"oai:opus.uleth.ca:10133/3492"},"canonical_url":"https://search.dev.ndltd.org/etd/lethbridge/oai:opus.uleth.ca:10133/3492","repository":{"repo_id":"lethbridge","name":"University of Lethbridge","base_url":"https://opus.uleth.ca/server/oai/request"},"display":{"title":"Structure and substrate specificity of myo-inositol phosphatases at atomic resolution","abstract":"Protein 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.","abstract_html":"Protein 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.","abstract_has_math":false,"creators":["Bruder, Lisza M."],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013","date_published":"2013","updated_at":"2026-07-27T20:02:08Z","subjects":["Inositol -- Research","Inositol phosphates -- Research","Dissertations, Academic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/3492"],"render_values":[{"text":"hdl:10133/3492","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":["2013"]},{"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","Dissertations, Academic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:10133/3492"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["Protein 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."]},{"key":"dc:title","label":"Title","values":["Structure and substrate specificity of myo-inositol phosphatases at atomic resolution"]}]}],"canonical_facts":{"dc:date.issued":["2013"],"dc:description.other":["Protein 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."],"dc:identifier":["hdl:10133/3492"],"dc:subject":["Inositol -- Research","Inositol phosphates -- Research","Dissertations, Academic"],"dc:title":["Structure and substrate specificity of myo-inositol phosphatases at atomic resolution"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T20:02:08Z"}