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The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme
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....
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| Format: | Thesis |
| Language: | English |
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Department of Medicine
2015
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| _version_ | 1867613286357270529 |
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| access_status_str | Open Access |
| author | Nkoe, Karabelo M |
| author2 | Sturrock, Edward D |
| author_browse | Nkoe, Karabelo M Sturrock, Edward D |
| author_facet | Sturrock, Edward D Nkoe, Karabelo M |
| author_sort | Nkoe, Karabelo M |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/13971 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:43.673Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2015 |
| publishDateRange | 2015 |
| publishDateSort | 2015 |
| publisher | Department of Medicine |
| publisherStr | Department of Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/13971 The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme Nkoe, Karabelo M Sturrock, Edward D Medicine 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. 2015-09-15T10:24:39Z 2015-09-15T10:24:39Z 2014 Master Thesis Masters MSc (Med) http://hdl.handle.net/11427/13971 eng application/pdf Department of Medicine Faculty of Health Sciences University of Cape Town |
| spellingShingle | Medicine Nkoe, Karabelo M The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme |
| thesis_degree_str | Master's |
| title | The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme |
| title_full | The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme |
| title_fullStr | The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme |
| title_full_unstemmed | The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme |
| title_short | The role of N-linked glycosylation on the structure and function of somatic angiotensin-converting enzyme |
| title_sort | role of n linked glycosylation on the structure and function of somatic angiotensin converting enzyme |
| topic | Medicine |
| url | http://hdl.handle.net/11427/13971 |
| work_keys_str_mv | AT nkoekarabelom theroleofnlinkedglycosylationonthestructureandfunctionofsomaticangiotensinconvertingenzyme AT nkoekarabelom roleofnlinkedglycosylationonthestructureandfunctionofsomaticangiotensinconvertingenzyme |