Professor Ed Sturrock

Country: South Africa

Institution: University of Cape Town

Research Areas: Protease structure/function and CVD drug discovery

Lab Website: www.idm.uct.ac.za/Edward_Sturrock#group

Proteases play an important role in a variety of biological processes ranging from digestion through to hormone activation and apoptosis. We are particularly interested in the metalloprotease angiotensin converting enzyme (ACE) that cleaves a wide variety of physiologically relevant substrates; including vasoregulatory peptides angiotensin I and bradykinin, the anti-fibrotic agent N-acetyl-SDKP, the neurotransmitter substance P and the adhesion molecule amyloid β peptide. Since ACE is primarily involved in the production of the vasoconstrictor angiotensin II, ACE has become a well-validated therapeutic target for hypertension, congestive heart failure, myocardial infarction and renal disease. There are two forms of the enzyme: a somatic form of 150-180 kDa and a smaller germinal isoform of 100-110 kDa which is expressed in the testes. Unlike nearly all zinc metallopeptidases the somatic enzyme has two homologous catalytic sites that display subtle differences. Our group has solved the structures of the ACE C- and N-terminal domains complexed with various clinically important inhibitors (as well as novel domain selective inhibitors), which has in turn opened the door to: 1) a better understanding of the structure-function relationships of each domain; and 2) the structure-based design of the next generation of domain specific ACE inhibitors for hypertension and heart failure.