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Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme
Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that plays an important role in vascular function; with ACE inhibitors being clinically utilised in the treatment of cardiovascular disease and diabetic nephropathy. Somatic ACE consists of two homologous catalytically active domains (de...
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| Format: | Thesis |
| Language: | English |
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Division of Medical Biochemistry
2015
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| _version_ | 1867613275861024768 |
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| access_status_str | Open Access |
| author | Douglas, Ross Gavin |
| author2 | Sturrock, Edward D |
| author_browse | Douglas, Ross Gavin Sturrock, Edward D |
| author_facet | Sturrock, Edward D Douglas, Ross Gavin |
| author_sort | Douglas, Ross Gavin |
| collection | Thesis |
| description | Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that plays an important role in vascular function; with ACE inhibitors being clinically utilised in the treatment of cardiovascular disease and diabetic nephropathy. Somatic ACE consists of two homologous catalytically active domains (designated N- and C-domains) that share high overall sequence identity and structural topology. Despite the high degree of similarity between domains, each domain displays differences in substrate processing and inhibitor binding abilities. This suggests that active site residues differing between the two domains could provide unique interactions within the N-domain that allow for N-selective binding and processing. Literature reports of ACE crystal structures and studies with substrate and inhibitor analogues have implicated unique residues present in the S2 and S2' subsites in providing important interactions for N-selectivity. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/11786 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:33:33.643Z |
| 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 | Division of Medical Biochemistry |
| publisherStr | Division of Medical Biochemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/11786 Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme Douglas, Ross Gavin Sturrock, Edward D Medical Biochemistry Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that plays an important role in vascular function; with ACE inhibitors being clinically utilised in the treatment of cardiovascular disease and diabetic nephropathy. Somatic ACE consists of two homologous catalytically active domains (designated N- and C-domains) that share high overall sequence identity and structural topology. Despite the high degree of similarity between domains, each domain displays differences in substrate processing and inhibitor binding abilities. This suggests that active site residues differing between the two domains could provide unique interactions within the N-domain that allow for N-selective binding and processing. Literature reports of ACE crystal structures and studies with substrate and inhibitor analogues have implicated unique residues present in the S2 and S2' subsites in providing important interactions for N-selectivity. 2015-01-08T19:59:58Z 2015-01-08T19:59:58Z 2011 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/11786 eng application/pdf Division of Medical Biochemistry Faculty of Health Sciences University of Cape Town |
| spellingShingle | Medical Biochemistry Douglas, Ross Gavin Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme |
| thesis_degree_str | Doctoral |
| title | Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme |
| title_full | Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme |
| title_fullStr | Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme |
| title_full_unstemmed | Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme |
| title_short | Significance of active site residues in the n-domain selectivity of angiotensin-converting enzyme |
| title_sort | significance of active site residues in the n domain selectivity of angiotensin converting enzyme |
| topic | Medical Biochemistry |
| url | http://hdl.handle.net/11427/11786 |
| work_keys_str_mv | AT douglasrossgavin significanceofactivesiteresiduesinthendomainselectivityofangiotensinconvertingenzyme |