{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/13971"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/13971","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme","abstract":"Angiotensin converting enzyme (ACE) is a key regulator of blood pressure and comprised of two homologous domains (N- and C-domain), both of which are glycosylated. N-linked glycosylation is important for the processing, expression and stability of ACE, but it interferes with protein crystallization. Previously, the N-glycan site occupancy required for the expression and stability of the individual domains of ACE was determined using minimally glycosylated (MG) N- and C-domain isoforms. However the role of glycosylation in the structure and function of the full-length somatic ACE (sACE) has remained elusive. A novel MG-sACE mutant, comprised of previously characterized MG N- and C-domains was generated. Unfortunately, the protein was susceptible to limited proteolysis in the interdomain linker region, suggesting that key glycans might shield the linker region from proteolysis. Furthermore, a loss in expression of MG-sACE was observed. These observations prompted the investigation of the effect of N-glycosylation on protection from inter-domain linker proteolysis, expression and overall stability of sACE. These aims were addressed by generating a panel of sACE glycosylation mutants.","abstract_html":"Angiotensin converting enzyme (ACE) is a key regulator of blood pressure and comprised of two homologous domains (N- and C-domain), both of which are glycosylated. N-linked glycosylation is important for the processing, expression and stability of ACE, but it interferes with protein crystallization. Previously, the N-glycan site occupancy required for the expression and stability of the individual domains of ACE was determined using minimally glycosylated (MG) N- and C-domain isoforms. However the role of glycosylation in the structure and function of the full-length somatic ACE (sACE) has remained elusive. A novel MG-sACE mutant, comprised of previously characterized MG N- and C-domains was generated. Unfortunately, the protein was susceptible to limited proteolysis in the interdomain linker region, suggesting that key glycans might shield the linker region from proteolysis. Furthermore, a loss in expression of MG-sACE was observed. These observations prompted the investigation of the effect of N-glycosylation on protection from inter-domain linker proteolysis, expression and overall stability of sACE. These aims were addressed by generating a panel of sACE glycosylation mutants.","abstract_has_math":false,"creators":["Nkoe, Karabelo M"],"institution":"Department of Medicine","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Sturrock, Edward D"],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014","date_published":"2014","updated_at":"2026-07-22T22:23:16Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/13971","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Sturrock, Edward D"]},{"key":"dc:creator","label":"Author","values":["Nkoe, Karabelo M"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-09-15T10:24:39Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-09-15T10:24:39Z"]},{"key":"dc:date.issued","label":"Date","values":["2014"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Medicine"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cape Town"]},{"key":"dc:type","label":"Dc Type","values":["Master Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Masters"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["MSc (Med)"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11427/13971"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Angiotensin converting enzyme (ACE) is a key regulator of blood pressure and comprised of two homologous domains (N- and C-domain), both of which are glycosylated. N-linked glycosylation is important for the processing, expression and stability of ACE, but it interferes with protein crystallization. Previously, the N-glycan site occupancy required for the expression and stability of the individual domains of ACE was determined using minimally glycosylated (MG) N- and C-domain isoforms. However the role of glycosylation in the structure and function of the full-length somatic ACE (sACE) has remained elusive. A novel MG-sACE mutant, comprised of previously characterized MG N- and C-domains was generated. Unfortunately, the protein was susceptible to limited proteolysis in the interdomain linker region, suggesting that key glycans might shield the linker region from proteolysis. Furthermore, a loss in expression of MG-sACE was observed. These observations prompted the investigation of the effect of N-glycosylation on protection from inter-domain linker proteolysis, expression and overall stability of sACE. These aims were addressed by generating a panel of sACE glycosylation mutants."]},{"key":"dc:title","label":"Title","values":["The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme"]}]}],"canonical_facts":{"dc:contributor.advisor":["Sturrock, Edward D"],"dc:creator":["Nkoe, Karabelo M"],"dc:date.accessioned":["2015-09-15T10:24:39Z"],"dc:date.available":["2015-09-15T10:24:39Z"],"dc:date.issued":["2014"],"dc:description.abstract":["Angiotensin converting enzyme (ACE) is a key regulator of blood pressure and comprised of two homologous domains (N- and C-domain), both of which are glycosylated. N-linked glycosylation is important for the processing, expression and stability of ACE, but it interferes with protein crystallization. Previously, the N-glycan site occupancy required for the expression and stability of the individual domains of ACE was determined using minimally glycosylated (MG) N- and C-domain isoforms. However the role of glycosylation in the structure and function of the full-length somatic ACE (sACE) has remained elusive. A novel MG-sACE mutant, comprised of previously characterized MG N- and C-domains was generated. Unfortunately, the protein was susceptible to limited proteolysis in the interdomain linker region, suggesting that key glycans might shield the linker region from proteolysis. Furthermore, a loss in expression of MG-sACE was observed. These observations prompted the investigation of the effect of N-glycosylation on protection from inter-domain linker proteolysis, expression and overall stability of sACE. These aims were addressed by generating a panel of sACE glycosylation mutants."],"dc:identifier.uri":["http://hdl.handle.net/11427/13971"],"dc:language.iso":["eng"],"dc:publisher.department":["Department of Medicine"],"dc:publisher.institution":["University of Cape Town"],"dc:title":["The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme"],"dc:type":["Master Thesis"],"dc:type.qualificationlevel":["Masters"],"dc:type.qualificationname":["MSc (Med)"]},"updated_at":"2026-07-22T22:23:16Z"}