Molecular reconstruction and homology modelling of the catalytic domain of the common ancestor of the haemostatic vitamin-K- dependent serine proteinases

摘要: The vitamin-K-dependent serine proteinases of coagulation have evolved by a process gene duplication and divergence, acquiring along the way considerable degree functional diversity that has equipped them for their different roles in haemostasis. cDNA sequences encoding catalytic domains early mammalian ancestors five factors (factors VII, IX X, protein C prothrombin) were reconstructed employing sequence data from range extant mammals using established phylogenies. putative common ancestor these proteins was then deduced phylogeny number respects those previously proposed. Factor is proposed to branched off on, followed prothrombin finally VII X. Significant differences mutation rates observed between within species; factor exhibited lower rate than other proteins, consistent with its emergence. Differences also species given an inverse correlation generation time. A biophysically plausible structure ancestral constructed comparative methods. Studies architecture this model provide new insights into evolution protein-binding specificity family proteins.