Species differences in amino acid sequences of Hageman factor and prekallikrein at region around scissile bond in activation

Abstract

The initial step in activation of the plasma kinin system is activation of Hageman factor (coagulation factor XII) and/or plasma prekallikrein. Two types of activation mechanisms, contact activation on a negatively charged surface and a cascade activation by exogenous proteases are known. Since these factors are serine protease zymogens, the activation of these molecules usually results from the cleavage of a particular -Arg-Ile(Val)- bond in either mechanism. Hence, these zymogens are regard to be substrates of their activator proteases. Sensitivity of the substrate for the protease basically depends on the amino acid sequence of six to eight residues around the scissile bond of the substrate. We found different activation efficiencies of these zymogens between human and guinea pig in both types of activation, and micro-heterogeneity of the sequence around the scissile bond among human, guinea pig and bovine Hageman factors, or between human and guinea pig prekallikreins. The sequence heterogeneity may explain the different activation efficiencies of these zymogens among mammalian species.