{"id":{"repo_id":"dundee","oai_identifier":"oai:discovery.dundee.ac.uk:studenttheses/ffddce97-0762-4c2b-96fb-d7a3666acffd"},"canonical_url":"https://search.dev.ndltd.org/etd/dundee/oai:discovery.dundee.ac.uk:studenttheses/ffddce97-0762-4c2b-96fb-d7a3666acffd","repository":{"repo_id":"dundee","name":"University of Dundee","base_url":"https://discovery.dundee.ac.uk/ws/oai"},"display":{"title":"Genetic encoding of a stable <i>O</i>-GlcNAc analogue","abstract":"Attachment of N-acetylglucosamine to hydroxyl groups of serine and threonine residues of intracellular proteins is known as <i>O</i>-GlcNAcylation, an essential posttranslational event in mammals and most other metazoa, catalysed by a unique <i>O</i>-GlcNAc transferase (OGT) and removed by an <i>O</i>-GlcNAc hydrolase (OGA). Despite the existence of a single writer/eraser pair, proteomic studies have identified over 4000 O-GlcNAcylated proteins in the nucleus, cytoplasm and mitochondria of various organisms, ranging from <i>C. elegans </i>to human. However, the molecular and biological mechanistic consequences of site-specific <i>O</i>-GlcNAcylation have been understudied due to the lack of appropriate tools. The function of <i>O</i>-GlcNAc modification in the context of specific sites in vivo is usually examined by a loss-offunction Ser/Thr to Ala mutation. The only available tool to study gain-of-function <i>O</i>-GlcNAcylation in vivo is OGA inhibition, which causes global elevation of <i>O</i>-GlcNAcylation levels, complicating the dissection of site-specific modification. This thesis describes the development of approaches to study <i>O</i>-GlcNAcylation in a protein and site-specific manner. Due to the labile nature of <i>O</i>-GlcNAc and susceptibility to OGA hydrolysis, methods for site-targeted incorporation of its non-hydrolysable analogue were explored.","abstract_html":"Attachment of N-acetylglucosamine to hydroxyl groups of serine and threonine residues of intracellular proteins is known as &lt;i&gt;O&lt;/i&gt;-GlcNAcylation, an essential posttranslational event in mammals and most other metazoa, catalysed by a unique &lt;i&gt;O&lt;/i&gt;-GlcNAc transferase (OGT) and removed by an &lt;i&gt;O&lt;/i&gt;-GlcNAc hydrolase (OGA). Despite the existence of a single writer/eraser pair, proteomic studies have identified over 4000 O-GlcNAcylated proteins in the nucleus, cytoplasm and mitochondria of various organisms, ranging from &lt;i&gt;C. elegans &lt;/i&gt;to human. However, the molecular and biological mechanistic consequences of site-specific &lt;i&gt;O&lt;/i&gt;-GlcNAcylation have been understudied due to the lack of appropriate tools. The function of &lt;i&gt;O&lt;/i&gt;-GlcNAc modification in the context of specific sites in vivo is usually examined by a loss-offunction Ser/Thr to Ala mutation. The only available tool to study gain-of-function &lt;i&gt;O&lt;/i&gt;-GlcNAcylation in vivo is OGA inhibition, which causes global elevation of &lt;i&gt;O&lt;/i&gt;-GlcNAcylation levels, complicating the dissection of site-specific modification. This thesis describes the development of approaches to study &lt;i&gt;O&lt;/i&gt;-GlcNAcylation in a protein and site-specific manner. Due to the labile nature of &lt;i&gt;O&lt;/i&gt;-GlcNAc and susceptibility to OGA hydrolysis, methods for site-targeted incorporation of its non-hydrolysable analogue were explored.","abstract_has_math":false,"creators":["Gorelik, Andrii"],"institution":"University of Dundee","degree_name":"Doctor of Philosophy","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["van Aalten, Daan"],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018","date_published":"2018","updated_at":"2026-07-24T02:08:39Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/ffddce97-0762-4c2b-96fb-d7a3666acffd"],"render_values":[{"text":"oai:discovery.dundee.ac.uk:studenttheses/ffddce97-0762-4c2b-96fb-d7a3666acffd","href":null,"code":true}]}]},"links":{"outbound_url":"https://discovery.dundee.ac.uk/en/studentTheses/ffddce97-0762-4c2b-96fb-d7a3666acffd","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["van Aalten, Daan"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["Wellcome Trust"]},{"key":"dc:creator","label":"Author","values":["Gorelik, Andrii"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018"]},{"key":"dc:date.issued","label":"Date","values":["2018"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Gene Regulation and Expression"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Dundee"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.dundee.ac.uk/en/studentTheses/ffddce97-0762-4c2b-96fb-d7a3666acffd"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights.embargodate","label":"Dc Rights Embargodate","values":["2021-11-30"]},{"key":"dc:rights.embargoreason","label":"Dc Rights Embargoreason","values":["/dk/atira/pure/core/document/studentthesisembargoreason/commercialexploitation"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:discovery.dundee.ac.uk:studenttheses/ffddce97-0762-4c2b-96fb-d7a3666acffd","https://discovery.dundee.ac.uk/en/studentTheses/ffddce97-0762-4c2b-96fb-d7a3666acffd"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.dundee.ac.uk/files/29187379/Andrii_Gorelik_Thesis_Final.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Attachment of N-acetylglucosamine to hydroxyl groups of serine and threonine residues of intracellular proteins is known as <i>O</i>-GlcNAcylation, an essential posttranslational event in mammals and most other metazoa, catalysed by a unique <i>O</i>-GlcNAc transferase (OGT) and removed by an <i>O</i>-GlcNAc hydrolase (OGA). Despite the existence of a single writer/eraser pair, proteomic studies have identified over 4000 O-GlcNAcylated proteins in the nucleus, cytoplasm and mitochondria of various organisms, ranging from <i>C. elegans </i>to human. However, the molecular and biological mechanistic consequences of site-specific <i>O</i>-GlcNAcylation have been understudied due to the lack of appropriate tools. The function of <i>O</i>-GlcNAc modification in the context of specific sites in vivo is usually examined by a loss-offunction Ser/Thr to Ala mutation. The only available tool to study gain-of-function <i>O</i>-GlcNAcylation in vivo is OGA inhibition, which causes global elevation of <i>O</i>-GlcNAcylation levels, complicating the dissection of site-specific modification. This thesis describes the development of approaches to study <i>O</i>-GlcNAcylation in a protein and site-specific manner. Due to the labile nature of <i>O</i>-GlcNAc and susceptibility to OGA hydrolysis, methods for site-targeted incorporation of its non-hydrolysable analogue were explored."]},{"key":"dc:title","label":"Title","values":["Genetic encoding of a stable <i>O</i>-GlcNAc analogue"]}]}],"canonical_facts":{"dc:contributor.advisor":["van Aalten, Daan"],"dc:contributor.sponsor":["Wellcome Trust"],"dc:creator":["Gorelik, Andrii"],"dc:date":["2018"],"dc:date.issued":["2018"],"dc:description.abstract":["Attachment of N-acetylglucosamine to hydroxyl groups of serine and threonine residues of intracellular proteins is known as <i>O</i>-GlcNAcylation, an essential posttranslational event in mammals and most other metazoa, catalysed by a unique <i>O</i>-GlcNAc transferase (OGT) and removed by an <i>O</i>-GlcNAc hydrolase (OGA). 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