A paper entitled “Autoactivation of thrombin precursors” by Nicola Pozzi, Ph.D. and the Di Cera lab will be published in the April 16 edition of The Journal of Biological Chemistry. The cover of the journal will feature a figure created by Tracey Baird, showing the crystal structures of the mutant S195A prethrombin-2 (cyan) and thrombin (gold) bound to argatroban (yellow sticks).
The paper discusses new findings showing that thrombin zymogen precursors are capable of catalytic activity and autoactivation. Activity of the mature thrombin protease is regulated by conformational selection in the trypsin fold, which could unlock autoactivation of the zymogen. Both the zymogen and protease exist in equilibrium between the active and inactive forms, which helps regulate the catalytic activity of the protease and could unlock activity of the zymogen. The production of enzymes through zymogen autoactivation could be applied to many clinically relevant trypsin-like proteases.