How the Serpin protein traps the digestive powers of the enzyme Serine Protease
Perhaps the most spectacular motion of any known protein is the springing of the trap known as the Serine Protease Inhibitor, also known as Serpin, a name that perhaps might be better suited to a protege of Darth Vader.
To understand what Serpin does, you will have to know what Serine Protease does. Serine Protease is one of those awesomely destructive enzymes in our biological arsenal, whose sole purpose is to digest other protein. When cells spit out Serine Protease, the Protease goes about its merry way chopping up every protein it can find. Specifically it looks for dangling loops of another protein (green), binds to it, then cuts it at the cleavage site (purple).
The Serine Proteases constitute an important but dangerous class of enzymes that destroys other proteins. Indeed, one of the best known analysis of Proteases is called the gladiator assay. In the Gladiator assay, different proteases are mixed in a test-tube and the survival rate of the different proteases against each other are measured. A vial of Serine Protease will eventually cut itself up in an act of unstoppable kamikaze.
So how do our digestive cells control this necessary but dangerous molecule? This is where the Serpin comes in. Inside our digestive cells, a store of of Serpin molecules is kept. When enough digestion has deemed to have occurred, the Serpin molecules are released to mix in with the Serine Proteases. Each Serpin is exquisitely designed to have a dangling, easily digestible loop.
This loop is easily bound to a Serine Protease, mimicking a loose loop of another protein. Upon binding, the Serine Protease will try to cut the loop.
When the Serine Protease cuts the juicy looking loop of the Serpin, Serpin will snap back onto the Serine Protease and wrap itself around the gaping mouth of the Serine Protease, thereby shutting down the digestive activity of the Serine Protease.
The springing of the Serpin trap upon Serine Protease is one of the most extravagant conformational change known to structural biology. Much of this motion is a complete mystery in terms of conventional protein conformational changes.
First the motion involves the Serpin flipping the Serine Protease from one end of the Serpin to another.
Second, part of the juicy loop of Serpin gets inserted into one of the beta-sheets of the Serpin. The beta-sheet must somehow be ripped open and then seal up around the loop. This is difficult to understand because it's typically accepted that beta-sheets are stable structures that define the overall architecture of the protein.
Finally, a careful comparison of the before state to the after state of the now inactivated Serine Protease shows that the mouth of Serine Protease gets mashed up and completely distorted upon the springing on the trap.
Although we have structures of the beginning and end of this motion, we don't know the chemistry and thermodynamics involved, none of the intermediate details are known. Unraveling the detailed mechanics of this motion will be one of the great challenges of protein chemistry.