Ions

In the previous steps we have several times seen ions. An example that we studied a bit more extensively is the zinc in the active site of some proteases. Here we will extend our ion quest .

Figure 39. The structure of 1dxg. Get the cleaned file DXG.pdb from the files list and load it in YASARA. You see two molecules. Both bind an iron.

Make a full description of the Fe binding site, including all nearby hydrogen bonds, including hydrogen bonds made by the S_γ  in the cysteines. Also answer all questions that have not been raised (fold, multimericity, relative position of Fe sites, function, which species have it, strange distributions of amino acids, etcetera).

Question 29: Which is the best known iron binding protein in your body? And how does it bind its iron?

Figure 40. Periodic system. So far, we have seen Calcium binding for protein stability, Zn binding in an active site, and now Iron binding in a protein that has 'something to do' with electrons. Why is that? Why don't we see calcium in an active site or Iron binding for stability?

Look at the MESPEUS database and answer these Questions(perhaps let each group look at one problem because MESPEUS is not very fast...):
(Remember to write down PDB file names of interesting entries, you will need them later on; read all questions before starting to answer them)!

• Ions can have a role in stability and function. Find some examples of both.
• Find an example of an ion that in one enzyme is functional, and in another has a stabilizing role.
• What is normally the role of Calcium?
• What is most often the role of Magnesium?
• Which metal ions are commonly included in multi-vitamin tablets?
• Why is it dangerous to do a simple text search in the PDB if you are looking for weird ions in enzyme structures?
• Find the preferred residues to bind: Na, Ca, Mg, Cu, Zn, Fe, Pb.

Now find one case each "clean" of Ca binding, functional Zn, and structural Zn. Describe the ion binding geometry. What are the ion - binder distances, angles, etc. And how would you describe the site (trigonal bi-pyramid, octahedron, etc).

Ion channels are a special class of proteins in this chapter. They interact only very briefly with their passing ions. Look at this semi-movie about an ion channel and answer the question (the movie has sound...):

Question 30: Why does a channel for potassium ion not let trough any sodium ions (and vice versa)?

Question 31:

• Why don't we see calcium in an active site or Iron binding for stability?
• Which are the preferred residues to bind: Na, Ca, Mg, Cu, Zn, Fe, Pb.
• Why is it dangerous to do a simple text search in the PDB if you are looking for weird ions in enzyme structures?