The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme

dc.contributor.advisorSturrock, Edward Den_ZA
dc.contributor.authorNkoe, Karabelo Men_ZA
dc.date.accessioned2015-09-15T10:24:39Z
dc.date.available2015-09-15T10:24:39Z
dc.date.issued2014en_ZA
dc.description.abstractAngiotensin 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.en_ZA
dc.identifier.apacitationNkoe, K. M. (2014). <i>The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Medicine. Retrieved from http://hdl.handle.net/11427/13971en_ZA
dc.identifier.chicagocitationNkoe, Karabelo M. <i>"The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2014. http://hdl.handle.net/11427/13971en_ZA
dc.identifier.citationNkoe, K. 2014. The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Nkoe, Karabelo M AB - 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. DA - 2014 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme TI - The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme UR - http://hdl.handle.net/11427/13971 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13971
dc.identifier.vancouvercitationNkoe KM. The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Medicine, 2014 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/13971en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherMedicineen_ZA
dc.titleThe role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzymeen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc (Med)en_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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