Three-dimensional structure, specificity and catalytic mechanism of renin

Renin is an aspartyl proteinase that catalyses the first, and rate-limiting, step in the conversion of angiotensinogen to the hormone angiotensin II. The catalysis is highly specific, and plays an important physiological part in the regulation of blood pressure. For this reason inhibitors of renin are of potential value in the treatment of certain forms of hypertension. Although progress has been made in the design of inhibitors for clinical use by modification of angiotensinogen sequences, and as pepstatin analogues or with reduced peptide bonds, we have now provided the basis for a more rational approach by the use of interactive computer graphics techniques to build a three-dimensional model of renin. The model is based on the three-dimensional structure of endothia pepsin and the primary structure of mouse renin, which is very similar to that of the human enzyme. We show that renin may have a three-dimensional structure similar to that of other aspartyl proteinases.