Human α2-antiplasmin is a member of the serine protease inhibitor (serpin) protein superfamily and it is the primary irreversible inhibitor of the fibrinolytic protease plasmin. The unique functions of α2-antiplasmin are attributed to its N-terminal (42-residues) and C-terminal (55-residue) extensions from the serpin core (1). α2-antiplasmin cross-links to fibrin clot by its N-terminal extensions; whereas the C-terminal extension contains several conserved charged residues that are believed to be important for the association of α2-antiplasmin and plasminogen (2-4). It is estimated that around 30% of plasminogen forms reversible complex with α2-antiplasmin in the circulation. This allows α2-antiplasmin to regulate fibrinolysis by reducing the binding of plasminogen to fibrin clot, which is essential for the activation of plasminogen to plasmin.

We aim to study the molecular interaction of α2-antiplasmin and plasminogen. Thus far we have successfully crystallized and determined the structure of recombinant human α2-antiplasmin.  Our best α2-antiplasmin crystals diffracted to 3.2Å at the Australian Synchrotron (MX2 beamline). Molecular replacement using the structure of mouse α2-antiplasmin was successfully performed (5). However the electron density for the termini regions is not readily interpretable. The current study focuses on methods to improve the resolution of the crystal diffraction data and gain insights on the possible molecular mechanism of α2-antiplasmin-plasminogen complex formation.