For Friday Sept 29th,
Barrick et al. (1997) “A test of the role of the proximal histidines in the Perutz model for cooperativity in haemoglobin,” Nature Structural Biology, 4, 78-83.
1) Define homotropic allosteric interactions and heterotropic allosteric interactions.
2) Which histidine (proximal or distal) directly interacts with O2?
3) What are the three observable changes that proximal detachment should produce?
4) In Figure 2, three of the haemoglobin species have hyperbolic binding curves, and one has a sigmoidal binding curve. What does the curve shape indicate?
5) Why have the authors examined the binding of n-butyl isocyanide to haemoglobin?
6) The Hill coefficient for aH87G is less than unity. How do the authors rationalize this observation? (The answer is not anti-cooperativity.)
7) Approximately how much does the proximal coupling mechanism contribute to the total interaction energy between haems?
8) Where does IHP bind and what is its effect on ligand affinity?
9) What technique have the authors used to determine the structural state (T or R) of haemoglobin and the haemoglobin mutants?
10) What is one plausible pathway for the residual cooperativity seen in the proximally detached haemoglobin mutants?