ANGIOTENSINOGEN CLEAVAGE BY RENIN - IMPORTANCE OF A STRUCTURALLY CONSTRAINED N-TERMINUS

Angiotensinogen, a plasma serpin, functions as a donor of the decapept ide angiotensin I, which is cleaved from the N-terminus by renin, To a ssess the contribution of the serpin framework to peptide cleavage we produced a chimaeric molecule of alpha(1)-antitrypsin carrying the ang iotensinogen N-terminus and determined the kinetic parameters for angi otensin I release, The K-m for plasma angiotensinogen was 18-fold lowe r than for the chiroaeric protein while the catalytic efficiency was f our-fold higher. We also show that Cys-18 participates in a disulphide bond and propose that constraints on the N-terminus profoundly affect the interaction with renin. (C) 1998 Federation of European Biochemic al Societies.