Problem Set #8: Metalloproteins

Due November 11 at the beginning of class



1.  November: a time for something fun and different.  For an artistic/colorful/fun display that I will hang up on the wall on the ground floor of Carr, I would like you to demonstrate to your fellow science students how cool protein structures are!  Choose a protein from PDB’s “Molecule of the Month” list (, read about it, and use Rasmol or a program of your choice to make a cool pretty picture of it.  Then, write one or more haiku about the protein (there are several examples on the www).  Make a collage with your picture and haiku.   I will award prizes to the most entertaining ones.



2.  As we discussed yesterday, ferritin is an iron storage protein.  Basically, it functions as a giant ball that sequesters Fe3+ by polymerizing it with oxygen-rich anions (sulfate, phosphate, hydroxide).  In the PDB, look at file 1AEW.  If you download it directly into RasMol, you will see just one chain, but ferritin is made up of a bunch of identical chains.  So, when you have pulled up 1AEW in the PDB, look to the left-hand margin.  Under “other resources” go to the EBI MSD Macromolecule File Server, which will give you the quarternary structure version of 1AEW.  Save it on the desktop, change the filename to “.pdb” and open it in RasMol.


Describe the shape and symmetry of ferritin to me at some length and specificity.   What is this shape called? How many symmetry axes, and of what kind of symmetry (Mirror planes? Rotational symmetry? 2, 3, 4, or 5-fold?) Discuss the number of chains and sketch out their relation to the edges, faces, and vertices of this regular polyhedron.


A pore at the 3-fold symmetry axis is proposed to be the place where Fe(II) leaves through after it is reduced. Is this pore polar or nonpolar?  What kinds of side chains are found here?  In this structure, there are heteroatoms in the pore.  What are they, why are they there, and to what side chains might they be attached?


Using “slab” mode, determine what is the thickness of the protein “coat” and inner diameter of the ferritin core.  What then would the approximate volume of the inside cavity be, in cubic Ćngstroms?


Which is more charged, the inside or the outside of the protein?  Which is more hydrophobic?  How is that different than most proteins? Why is it like that?

3. In chymotrypsin, a mutant was constructed with Ser189, which is at the bottom of the main substrate specificity pocket, changed to Glu.  What effect would you predict for this Ser189 to Glu mutation?


4. Enzymes can only catalyze reactions that are thermodynamically favorable.  A particular reaction has a standard free energy change (DGŻ) that is positive (that is, unfavorable), and yet the reaction occurs inside the cell without being coupled to ATP or other energy-generating reaction.  How is this possible?


5. Your pet lobster has been sluggish and the vet suspects that he might be a bit anemic.  Should you supplement his diet with iron?


6. A novel putative electron-transport protein has been isolated.  When elemental analysis suggests that it contains only zinc, you argue that either the protein or the function cannot be right. Why not?


7. An important experiment in the history of biochemistry was the demonstration by Sumner that an enzyme, jack bean urease, could be crystallized. The fact that this crystalline enzyme was a pure protein was crucial to the arguments that enzymes were proteins.  Some fifity years later, it was discovered that urease contains two Ni2+ ions per protein molecule.  Comment on how this observation might have affected biochemistry had it been made some fifty years earlier.


8.  Which side chains would you predict to bind best to metal ions in proteins, and why?