HOMOLOGY MODELING OF THE CATALYTIC DOMAIN OF EARLY MAMMALIAN PROTEIN-C - EVOLUTION OF STRUCTURAL FEATURES

By means of a novel cDNA-based strategy employing the maximum parsimon y principle, we have previously deduced probable amino acid sequences for the catalytic domains of the early mammalian ancestors of each of the five extant vitamin K-dependent serine proteases of coagulation, a nd for their common ancestor from a still earlier stage of vertebrate evolution. In the present study, we employed one of these sequences to construct a molecular model of the catalytic domain of early mammalia n protein C and to explore its functional architecture. Following the domain's progression from the common ancestor of the vitamin K-depende nt serine proteases toward extant human protein C, this novel applicat ion of homology modelling to a reconstructed amino acid sequence has a llowed us to trace the evolution of structural features in a vital coa gulation protein.