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 (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.

Grantor dc:publisher.institution

Division of Medical Biochemistry

Year dc:date.issued

2011

Author dc:creator

• Douglas, Ross Gavin

Advisor dc:contributor.advisor

• Sturrock, Edward D

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/11786

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/11786