Angiotensinogen cleavage by renin: importance of a structurally constrained N-terminus
Abstract
Angiotensinogen, a plasma serpin, functions as a donor of the decapeptide angiotensin I, which is cleaved from the N-terminus by renin. To assess the contribution of the serpin framework to peptide cleavage we produced a chimaeric molecule of α 1-antitrypsin carrying the angiotensinogen N-terminus and determined the kinetic parameters for angiotensin I release. The K m for plasma angiotensinogen was 18-fold lower than for the chimaeric protein while the catalytic efficiency was four-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.
- Publication:
-
FEBS Letters
- Pub Date:
- January 1998
- DOI:
- 10.1016/S0014-5793(98)01145-4
- Bibcode:
- 1998FEBSL.436..267S
- Keywords:
-
- Angiotensinogen;
- Serpin;
- Hypertension;
- ACE;
- angiotensin-converting enzyme;
- AngAT;
- Ang-Antitrypsin;
- IPTG;
- isopropyl-β- d-thiogalactopyronoside;
- HPLC;
- high performance liquid chromatography