DW Lecture 3: Ligand Binding

Question 1

List the kinds of complementarity.

Answer 1

shape
electrostatic
hydrogen bonding
hydrophobic

Question 2

What is shape complementarity?

Answer 2

the absence of cavities between the ligand and the protein, which maximizes van der Waals interactions

Question 3

What is electrostatic complementarity?

Answer 3

a charged group in the binding site interacts with a group of the opposite charge in the ligand

Question 4

What is hydrogen bonding complementarity?

Answer 4

a hydrogen bond donor in the binding site interacts with a hydrogen bond acceptor in the ligand (or vice versa)
includes water-mediated interactions

Question 5

What is hydrophobic complementarity?

Answer 5

hydrophobic groups in the binding site interacts with hydrophobic groups in the ligand to protect each other from interacting with water

Question 6

How do you calculate the dissociation constant of a ligand-receptor interaction?

Answer 6

Kd = ( [P] [L] ) / [PL]

Question 7

What is the dissociation constant?

Answer 7

Kd

the equilibrium constant for the dissociation reaction

Question 8

What is the dissociation constant when half of the protein is bound to the ligand?

Answer 8

[P] = [PL]
and
Kd = [L]

Question 9

Describe the relationship between Kd and affinity of a ligand for a protein.

Answer 9

the lower the Kd the higher the affinity of a ligand for a protien (because it takes a smaller amount of ligand to half-saturate its binding partner)

Question 10

Describe the binding of oxygen in red blood cells.

Answer 10

HbA is composed of two alpha and two beta chains each with a heme prosthetic group
oxygen binds to the heme by interacting with Fe2+ in the heme group and forming a H bond with a histidine in globin

Question 11

What is the tense (T) state?

Answer 11

where hemoglobin has a low affinity for O2

Question 12

What is the relaxed (R) state?

Answer 12

where hemoglobin has a high affinity for O2

Question 13

Describe the cooperative binding of oxygen to hemoglobin.

Answer 13

oxygen binds hemoglobin in a way where each molecule of oxygen that binds increases the affinity of other hemes in the same protein for oxygen

Question 14

Why is cooperative binding important for hemoglobin?

Answer 14

because it allows for hemoglobin to become completely saturated with oxygen in the lungs and release it in the tissues

Question 15

What are allosteric effectors?

Answer 15

molecules that bind to a protein on one site and cause a conformational change in the protein that affects its function at a distant site

Question 16

What molecules allosterically affect binding of oxygen to hemoglobin?

Answer 16

oxygen itself
CO2
protons
2,3-bisphosphoglycerate (2,3-BPG)

Question 17

How does CO2 concentration affect the binding of O2?

Answer 17

1. high concentrations of dissolved CO2 shifts the equilibrium of the bicarb reaction towards bicarb plus protons
   lowering the pH decreases affinity of hemoglobin for O2
2. binding of CO2 to hemoglobin decreases its affinity for O2

Question 18

How do protons affect the binding of O2 to hemoglobin?

Answer 18

lowering the pH decreases the affinity of hemoglobin for O2

more protons makes it acidic and a lower pH

Question 19

What is the Bohr effect?

Answer 19

lowering the pH causes a decrease in affinity of hemoglobin for O2
this allows for more oxygen to be released in active tissues (where the pH is low)

Question 20

How does 2,3-BPG affect the binding of O2 to hemoglobin?

Answer 20

binding of 2,3-BPG to heme decreases its affinity for O2

results in a release of O2 from hemoglobin at higher partial pressures of O2

Question 21

What affects 2,3-BPG concentrations?

Answer 21

anemia and chronic hypoxia (due to lung disease) increase 2,3-BPG concentration
increases in response to decreases in partial pressure of O2 in the air (allows for adjustment to high altitude)

Question 22

How does 2,3-BPG interact differently with HbA and HbF?

Answer 22

does not bind strongly to HbF resulting in HbF having a higher affinity for oxygen

Question 23

Why does HbF have a higher affinity for O2?

Answer 23

increases efficiency in transferring O2 from maternal red blood cells to fetal red blood cells