Relationships between structure and function of tissue-type plasminogen activator

This mini-review deals with structure-function relationships of human tissue-type plasminogen activator. The enzyme consists of a single polypeptide chain of 527 amino acids. A two-chain form is produced by proteolytic cleavage of the Arg 275-Ile 276 peptide bond. The aminoterminal heavy or A-chain consists of a finger domain, a growth factor domain and two kringle domains. The carboxyterminal light or B-chain contains the active site and is homologous to the catalytic chains of other serine proteases. The light chain is able to activate plasminogen, but requires the heavy chain for fibrin-binding and fibrin-stimulation. Particularly, the finger domain and kringle 2 of the heavy chain are involved in the interaction with fibrin. Other specific properties of the plasminogen activator, such as its rapid hepatic clearance and its inhibition by plasminogen activator inhibitors have not yet been related to specific domains in the protein structure.