Angiotensin Converting Enzyme (ACE) Site-directed Mutations Designed to Study the Enzyme Interaction with its Specific Inhibitors

ACE is considered a key enzyme of the renin angiotensin system (RAS), which is involved in blood pressure regulation and electrolyte and fluid homeostasis. ACE is responsible for generating the most important vasoconstrictor peptide of the RAS, angiotensin II. The use of ACE inhibitors and antagonists of angiotensin II receptors are strategies for the treatment of hypertension. Considering its physiological importance, ACE has being the target of many studies which seek for better understanding of its structure and its interaction with specific inhibitors. The aim of this study is the development of site-directed mutations in order to investigate whether modifications in the target amino acid residues may compromise the enzyme/inhibitor interaction through the purification and characterization of ACE mutants. The target amino acid residues were chosen based on the structural studies of the enzyme and are strong candidates for interaction with ACE inhibitors. Oligonucleotides for the change of the target a...