Myoglobin and Hemoglobin

Question 1

Describe the structure of myoglobin

Answer 1

• 8 alpha helices

Question 2

Describe how the heme group is packed in myoglobin

Answer 2

• heme group is packed between hydrophobic side chains (Val and Phe)

Question 3

What does fractional saturation of a protein mean?

Answer 3

• fraction of binding sites occupied by ligand L relative to the total available sites
• for O2 binding curves, fractional saturation is fraction of O2 binding sites occupied by O2

Question 4

What is p50?

Answer 4

• p50 is the partial pressure of oxygen when fractional saturation (Y) is 0.5

Question 5

Describe the structure of hemoglobin?

Answer 5

• 4 myoglobin like subunits
• 2 Hb chains are alpha chains, other two are beta chins

Question 6

How is the oxygen binding curve of hemoglobin different from that of myoglobin?

Answer 6

• for hemoglobin, the binding curve is sigmoidal due to cooperativity, which is not present in myoglobin
• cooperativity is cross-talk between the 4 subunits of hemoglobin

Question 7

What does hemoglobin’s oxygen affinity depend on?

Answer 7

• pH

Question 8

What type of symmetry does hemoglobin have?

Answer 8

C2

Question 9

What’s the difference between the T state and R state of hemoglobin?

Answer 9

• T state is deoxygenated, R state is oxygenated
• the transition between T and R does not change symmetry. it involves quarternary structural changes like a rotation of 15° of 2 lobes
• T state has several salt bridges that are broken in the transition

Question 10

If we have low O concentration, what state of hemoglobin is favored?

Answer 10

• T state is more energetically favorable

Question 11

How does O2 binding to heme occur in hemoglobin?

Answer 11

• The iron moves into the plane of the heme when O2 binds and heme becomes planar when O2 binds
• His acts as a lever and moves helix F
  salt bridges are changed between the subunits
• shift in pka of groups in the salt bridges causes proton release

Question 12

What does the Hill coefficient describe?

Answer 12

describes the amount of cooperativity

Question 13

If we have a large Hill coefficient, what does that mean for the oxygen binding curve?

Answer 13

• larger Hill, steeper the S-shaped oxygen binding Hill plot

Question 14

What is the official definition of cooperativity?

Answer 14

• a molecule with multiple binding sites, binding to one of those sites changes the binding specificity at other binding sites

Question 15

As pH decreases, what happens to the binding of O2?

Answer 15

• O2 binding decreases
• salt bridges that help stabilize the T state is formed by a histidine, as pH lowers, histidine becomes more protonated and it favors the deoxygenated state, which leads to less binding, so curve moves more to the right

Question 16

When would a cell lower its pH?

Answer 16

• cell is burning a lot of O2

Question 17

Describe the symmetric model of hemoglobin allostery?

Answer 17

• we assume that molecular symmetry is maintained
  hemoglobin cannot adopt an intermediate conformation. tetramer is either in T state of R state

Question 18

What is BPG’s effect on oxygen?

Answer 18

• at high altitudes, our bodies produce more BPG’s
• negatively charged BPG binds to the positive charges in the central cavity of hemoglobin, but only when it’s in the deoxygenated state (T)
• BPG binding stabilize the deoxygenated state of hemoglobin
• this decreases Hb’s affinity for O2, so more delivery of O2 from lung to tissue