Name a human protein that uses one or more metal ions. Answer
Locating metal ions is an alternative way to find the active site of enzymes. Take care: there are several other reasons why a metal ion can appear in a 3D structure of a protein, so do not rely blindly on this method to find the active site.
Reset Yasara by clicking File > New and then Yes. Load the file venom2.pdb as you have done before.
The zinc ion (Zn2+) is clearly visible as a purple ball in the appropriate representation. Use this ion to find the active site. Cheat: it's easier to use the sequence bar: Zn
is mentioned at the end of the sequence. If you click on Zn while
holding the Ctrl key, the protein will automatically
rotate so that you can see the ion.
Now that we know the active site, we can search for an antidote. To do this, we use the fact that enzymes work accordingly to a lock-and-key principle.
Explain briefly what the lock-and-key principle is. If necessary, draw a picture. Answer
You might know (maybe from experience), that a lock can be made useless if you insert something that does not belong there. The key does not fit anymore and the lock is broken. Our antidote will work according to the same principle. We are looking for a molecule that binds so
tightly to the venom that it cannot be released anymore. This will inactivate the
poison.
You have already seen interactions that cause the protein to fold in a particular way. The binding of the antidote depends on similar interactions. Therefore,
one should look for hydrogen bonds, hydrophobic interactions and ionic interactions. Of course, the antidote must also fit in the cavity.
Open Help > Play help movie > 6.8 Rattle snake poison > OK and watch the movie.
Click on Continue when the animation is over. You can keep looking at the molecule. Close the window (and click Yes) to go back to the main Yasara window.
You can see that a small molecule enters the active site and binds to our venom protein. This small molecule is called a ligand, and is made in such a way that it fits nicely in the protein cavity. However, it is made only of carbons, and will therefore not have many
strong interactions with the active site.
In the last part of this practicum, you will look at a couple of adapted versions of the ligand and decide which version is the best. The best ligand is the one that binds best to the protein. This may be a
potent antidote...
