Angiotensinogen cleavage by renin: importance of a structurally constrained N-terminus Academic Article uri icon

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 alpha1-antitrypsin carrying the angiotensinogen N-terminus and determined the kinetic parameters for angiotensin I release. The Km 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.

authors

  • Streatfeild-James, Rosa M
  • Williamson, David
  • Pike, Robert N
  • Tewksbury, Duane
  • Carrell, Robin W
  • Coughlin, Paul B

publication date

  • October 2, 1998

has subject area