Structural and Functional Studies of Human Plasminogen and Cofactors

Abstract

Plasminogen is the inactive precursor of Plasmin, a protease with diverse physiological roles such as the removal of blood clots and wound healing. Plasminogen/Plasmin are important therapeutic targets especially in stroke and heart attack but to date, the mechanism behind Plasminogen activation remains largely unclear. This thesis focuses on the studies of (co-)factors affecting Plasminogen activation via biophysical and biochemical methods. It was found that sugar modification (glycosylation) significantly impacts Plasminogen activation and furthermore, striking differences were observed when Plasminogen activators isolated from human and bacterial pathogen were compared. Overall, this work has advanced our understanding of the Plasminogen/Plasmin system.