Conservation and variability in the structures of serine proteinases of the chymotrypsin family

Abstract

The chymotrypsin-like serine proteinases are a widely divergent family of enzymes appearing in animals, bacteria and viruses. All comprise two homologous domains containing six-stranded beta-barrels, with the active site between the domains. What are the structural constraints to which these proteins have been subject during their evolution, and how have the molecules explored the limits these constraints impose? We have analysed the structures of 13 widely divergent serine proteinases determined by X-ray crystallography to high resolution and well refined. We have identified the regions of the molecule that evolution has preserved both within each of the two domains and in the interdomain interface. An alignment of the sequences is presented based on structural superpositions. From this we analyse the conserved structural patterns and the interactions crucial to maintaining the structure and the active side.