Editing Plasmin (section)

== Mechanism of plasmin inactivation ==

{{Unreferenced section|date=November 2016}}

Plasmin is inactivated by proteins such as [[Alpha-2-Macroglobulin|α2-macroglobulin]] and [[Alpha 2-antiplasmin|α2-antiplasmin]].<ref>{{cite journal | vauthors = Wu G, Quek AJ, Caradoc-Davies TT, Ekkel SM, Mazzitelli B, Whisstock JC, Law RH | title = Structural studies of plasmin inhibition | journal = Biochemical Society Transactions | volume = 47 | issue = 2 | pages = 541–557 | date = April 2019 | pmid = 30837322 | doi = 10.1042/bst20180211 | s2cid = 73463150 }}</ref> The mechanism of plasmin inactivation involves the cleavage of an α2-macroglobulin at the bait region (a segment of the aM that is particularly susceptible to proteolytic cleavage) by plasmin. This initiates a conformational change such that the α2-macroglobulin collapses about the plasmin. In the resulting α2-macroglobulin-plasmin complex, the active site of plasmin is [[Steric effects#Steric hindrance|sterically]] shielded, thus substantially decreasing the plasmin's access to protein substrates. Two additional events occur as a consequence of bait region cleavage, namely (i) a h-cysteinyl-g-glutamyl thiol ester of the α2-macroglobulin becomes highly reactive and (ii) a major conformational change exposes a conserved [[COOH-terminal]] receptor binding domain. The exposure of this receptor binding domain allows the α2-macroglobulin protease complex to bind to clearance receptors and be removed from circulation.