We intend to continue our studies on the molecular, structural, kinetic, and mechanistic properties of the angiotensinI-converting enzyme.
The specific aim of this grant are: 1) To obtain the limit peptide of the converting enzyme that contains some or all of the active-site residues and to sequence this peptide. 2) To study the chemical mechanism of the converting enzyme to establish whether an acyl-enzyme intermediate is formed. 3) To study the nature of the active site bindingr pocket subsites by the kinetic study of substrates and inhibitors; to study the phenomenon of substrate inhibition, the requirement for monovalent anions, and the significance of inhibition by cyanide and pyrophosphate. 4) To develop a substrate that can be used for an activity stain to detect very low levels of converting enzyme activity. 5) To continue to develop a biospecific affinity ligand for the converting enzyme and to continue to improve the general method of affinity chromatography purification. 6) To establish the existence of converting enzyme in brain tissue and other tissue sources such as cerebrospinal fluid and aminotic fluid. 7) To study the molecular and kinetic properties of the converting enzyme purified from different sources.
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