• Quaternary

EU name: 3D-501

 (From: ../step5 ) (Date: Aug 24 2016 ../step)

After completing the "Quarternary structure" part of the Structure section you will:
Know about the existence of different protein chains in one PDB file
Be able to identify interactions between the subunits in the protein quarternary structure
Understand that multimericity sometimes is needed for cooperativity and sometimes for activity

Many proteins only function as a complex mulimer containing multiple chains, additional groups, ions, lipis, waters, etc. Think for example of haemoglobin that consists of two α-chains and two β-chains, and all four chains have a haem-group bound. The level of the complete, active molecule is called the quaternary structure.

Triose Phosphate Isomerase Dimer

Figure 63. Load the file TIMD.pdb in yasara. This now is a dimer of the same TIM molecule you saw earlier. That monomer was a bit artificial because in real life TIM can only function as a dimer. This dimer contains two inhibitors (substrate analogs).

Question 82: Describe the interactions between the TIM monomers. Pay attention to functional aspects.
Hint: If a molecule functions as a dimer, then that normally means that there is some cooperativity, and that in turn requires communication between the partners in that cooperativity (in this case the two monomers).

Answer

EU name: 3D-502

 (From: ../step5 ) (Date: Aug 24 2016 ../step)

HIV Protease Dimer

Figure 64. Load the file HIV.pdb in yasara. This is the protease of HIV that helps it process its proteins. It was also the first target for AIDS related drug design.

Question 83: Start with all questions that were not asked, so what type of protease is this? What should it cleave, and why? Etcetera.

Answer

Question 84: Where do you think that the protein sits when it gets cleaved by the HIV protease?

Answer

Question 85: Compare the role of the monomers in the function of HIV protease with the role of each monomer in the TIM dimer.

Answer

EU name: 3D-503

 (From: ../step5 ) (Date: Aug 24 2016 ../step)

Alcohol Dehydrogenase Tetramer

Figure 65. Load the file BTO.pdb in yasara. This is a horse liver alcohol dehydrogenase tetramer complexed with NADH and a alcohol look-alike as inhibitor. I have no idea why a horse needs alcohol dehydrogenase because a horse cannot even open a can of beer, but I leave that question to the biologists among you.

Question 86: Start with all questions that were not asked. What reaction does this enzyme catalyse? Where does it do that? and why? What happens if a mutation has rendered that enzyme useless in my body? Etcetera.

Answer

Question 87: Describe the symmetry of this alcohol dehydrogenase multimer. In other words, if you only have one of the four monomers, which type(s) of symmetry operations would be needed to generate the other three?

Answer

Question 88: Take a look at the closest alcohol dehydrogenase dimer contacts. Can you describe them?

Answer