Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design

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dc.contributor.authorCorradi, Hazel R
dc.contributor.authorSchwager, Sylva L U
dc.contributor.authorNchinda, Aloysius T
dc.contributor.authorSturrock, Edward D
dc.contributor.authorAcharya, K Ravi
dc.date.accessioned2016-09-05T19:18:59Z
dc.date.available2016-09-05T19:18:59Z
dc.date.issued2006
dc.date.updated2016-09-05T11:38:53Z
dc.description.abstractHuman somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of “domain-specific” second-generation ACE inhibitors.en_ZA
dc.identifierhttp://dx.doi.org/10.1016/j.jmb.2006.01.048
dc.identifier.apacitationCorradi, H. R., Schwager, S. L. U., Nchinda, A. T., Sturrock, E. D., & Acharya, K. R. (2006). Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design. <i>Journal of Molecular Biology</i>, http://hdl.handle.net/11427/21678en_ZA
dc.identifier.chicagocitationCorradi, Hazel R, Sylva L U Schwager, Aloysius T Nchinda, Edward D Sturrock, and K Ravi Acharya "Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design." <i>Journal of Molecular Biology</i> (2006) http://hdl.handle.net/11427/21678en_ZA
dc.identifier.citationCorradi, H. R., Schwager, S. L., Nchinda, A. T., Sturrock, E. D., & Acharya, K. R. (2006). Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design. Journal of molecular biology, 357(3), 964-974.en_ZA
dc.identifier.issn0022-2836en_ZA
dc.identifier.ris TY - Journal Article AU - Corradi, Hazel R AU - Schwager, Sylva L U AU - Nchinda, Aloysius T AU - Sturrock, Edward D AU - Acharya, K Ravi AB - Human somatic angiotensin I-converting enzyme (sACE) is a key regulator of blood pressure and an important drug target for combating cardiovascular and renal disease. sACE comprises two homologous metallopeptidase domains, N and C, joined by an inter-domain linker. Both domains are capable of cleaving the two hemoregulatory peptides angiotensin I and bradykinin, but differ in their affinities for a range of other substrates and inhibitors. Previously we determined the structure of testis ACE (C domain); here we present the crystal structure of the N domain of sACE (both in the presence and absence of the antihypertensive drug lisinopril) in order to aid the understanding of how these two domains differ in specificity and function. In addition, the structure of most of the inter-domain linker allows us to propose relative domain positions for sACE that may contribute to the domain cooperativity. The structure now provides a platform for the design of “domain-specific” second-generation ACE inhibitors. DA - 2006 DB - OpenUCT DP - University of Cape Town J1 - Journal of Molecular Biology LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 SM - 0022-2836 T1 - Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design TI - Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design UR - http://hdl.handle.net/11427/21678 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/21678
dc.identifier.vancouvercitationCorradi HR, Schwager SLU, Nchinda AT, Sturrock ED, Acharya KR. Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design. Journal of Molecular Biology. 2006; http://hdl.handle.net/11427/21678.en_ZA
dc.languageengen_ZA
dc.publisherElsevieren_ZA
dc.publisher.institutionUniversity of Cape Town
dc.sourceJournal of Molecular Biologyen_ZA
dc.source.urihttp://www.journals.elsevier.com/journal-of-molecular-biology/
dc.subject.otherangiotensin I-converting enzyme
dc.subject.othercardiovascular disease
dc.subject.othercrystal structure
dc.subject.otherhypertension
dc.titleCrystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor designen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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