Some serpins are activated by cofactors. The the serpin <a href="//commons.wikimedia.org/w/index.php?title=Antithrombin&amp;action=edit&amp;redlink=1" class="new" title="Antithrombin (page does not exist)">antithrombin</a> has an RCL (blue) where the P1 arginine (blue sticks) points inwards, preventing protease binding. Binding of <a href="//commons.wikimedia.org/w/index.php?title=Heparin&amp;action=edit&amp;redlink=1" class="new" title="Heparin (page does not exist)">heparin</a> (green sticks) causes the P1 arginine residue to flip to an exposed position. The target protease (grey) then binds both the exposed P1 arginine as well as the heparin. The serpin then activates and heparin is released. (<span class="plainlinks"><a href="https://en.wikipedia.org/wiki/Protein_Data_Bank" class="extiw" title="w:Protein Data Bank">PDB</a>: <a rel="nofollow" class="external text" href="http://www.rcsb.org/pdb/explore/explore.do?structureId=2ANT">2ANT</a>, <a rel="nofollow" class="external text" href="http://www.rcsb.org/pdb/explore/explore.do?structureId=1TB6">1TB6</a>, <a rel="nofollow" class="external text" href="http://www.rcsb.org/pdb/explore/explore.do?structureId=1EZX">1EZX</a></span>​)
<a href="//commons.wikimedia.org/wiki/User:Evolution_and_evolvability" title="User:Evolution and evolvability">Thomas Shafee</a>
CC BY 4.0
<span class="int-own-work" lang="en">Own work</span>