Structure of angiotensin I-converting enzyme
| dc.contributor.author | Sturrock, E D | |
| dc.contributor.author | Natesh, R | |
| dc.contributor.author | van Rooyen, J M | |
| dc.contributor.author | Acharya, K R | |
| dc.date.accessioned | 2016-09-01T07:52:42Z | |
| dc.date.available | 2016-09-01T07:52:42Z | |
| dc.date.issued | 2004 | |
| dc.date.updated | 2016-08-30T10:41:51Z | |
| dc.description.abstract | Angiotensin-converting enzyme (ACE) is a zinc- and chloride-dependent metallopeptidase that plays a vital role in the metabolism of biologically active peptides. Until recently, much of the inhibitor design and mechanism of action of this ubiquitous enzyme was based on the structures of carboxypeptidase A and thermolysin. When compared to the recently solved structures of the testis isoform of ACE (tACE) and its Drosophila homologue (AnCE), carboxypeptidase A showed little structural homology outside of the active site, while thermolysin revealed significant but less marked overall similarity. The ellipsoid-shaped structure of tACE, which has a preponderance of α-helices, is characterised by a core channel that has a constriction approximately 10 Å from its opening where the zinc-binding active site is located. Comparison of the native protein with the inhibitor-bound form (lisinopril-tACE) does not reveal any striking differences in the conformation of the inhibitor binding site, disfavouring an open and closed configuration. However, the inhibitor complex does provide insights into the network of hydrogen-bonding and ionic interactions in the active site as well as the mechanism of ACE substrate hydrolysis. The three-dimensional structure of ACE now paves the way for the rational design of a new generation of domain-selective ACE inhibitors. | en_ZA |
| dc.identifier | http://dx.doi.org/10.1007/s00018-004-4239-0 | |
| dc.identifier.apacitation | Sturrock, E. D., Natesh, R., van Rooyen, J. M., & Acharya, K. R. (2004). Structure of angiotensin I-converting enzyme. <i>Cellular and Molecular Life Sciences</i>, http://hdl.handle.net/11427/21634 | en_ZA |
| dc.identifier.chicagocitation | Sturrock, E D, R Natesh, J M van Rooyen, and K R Acharya "Structure of angiotensin I-converting enzyme." <i>Cellular and Molecular Life Sciences</i> (2004) http://hdl.handle.net/11427/21634 | en_ZA |
| dc.identifier.citation | Sturrock, E. D., Natesh, R., Van Rooyen, J. M., & Acharya, K. R. (2004). Structure of angiotensin I-converting enzyme. Cellular and molecular life sciences, 61, 2677-2686. | en_ZA |
| dc.identifier.issn | 1420-682X | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Sturrock, E D AU - Natesh, R AU - van Rooyen, J M AU - Acharya, K R AB - Angiotensin-converting enzyme (ACE) is a zinc- and chloride-dependent metallopeptidase that plays a vital role in the metabolism of biologically active peptides. Until recently, much of the inhibitor design and mechanism of action of this ubiquitous enzyme was based on the structures of carboxypeptidase A and thermolysin. When compared to the recently solved structures of the testis isoform of ACE (tACE) and its Drosophila homologue (AnCE), carboxypeptidase A showed little structural homology outside of the active site, while thermolysin revealed significant but less marked overall similarity. The ellipsoid-shaped structure of tACE, which has a preponderance of α-helices, is characterised by a core channel that has a constriction approximately 10 Å from its opening where the zinc-binding active site is located. Comparison of the native protein with the inhibitor-bound form (lisinopril-tACE) does not reveal any striking differences in the conformation of the inhibitor binding site, disfavouring an open and closed configuration. However, the inhibitor complex does provide insights into the network of hydrogen-bonding and ionic interactions in the active site as well as the mechanism of ACE substrate hydrolysis. The three-dimensional structure of ACE now paves the way for the rational design of a new generation of domain-selective ACE inhibitors. DA - 2004 DB - OpenUCT DP - University of Cape Town J1 - Cellular and Molecular Life Sciences LK - https://open.uct.ac.za PB - University of Cape Town PY - 2004 SM - 1420-682X T1 - Structure of angiotensin I-converting enzyme TI - Structure of angiotensin I-converting enzyme UR - http://hdl.handle.net/11427/21634 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/21634 | |
| dc.identifier.vancouvercitation | Sturrock ED, Natesh R, van Rooyen JM, Acharya KR. Structure of angiotensin I-converting enzyme. Cellular and Molecular Life Sciences. 2004; http://hdl.handle.net/11427/21634. | en_ZA |
| dc.language | eng | en_ZA |
| dc.publisher | Springer | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.source | Cellular and Molecular Life Sciences | en_ZA |
| dc.source.uri | http://link.springer.com/journal/18 | |
| dc.subject.other | Metallopeptidase | |
| dc.subject.other | angiotensin I-converting enzyme | |
| dc.subject.other | Drosophila angiotensin converting enzyme homologu | |
| dc.title | Structure of angiotensin I-converting enzyme | en_ZA |
| dc.type | Journal Article | en_ZA |
| uct.type.filetype | Text | |
| uct.type.filetype | Image | |
| uct.type.publication | Research | en_ZA |
| uct.type.resource | Article | en_ZA |