DW Lecture 3: Ligand Binding Flashcards
List the kinds of complementarity.
shape
electrostatic
hydrogen bonding
hydrophobic
What is shape complementarity?
the absence of cavities between the ligand and the protein, which maximizes van der Waals interactions
What is electrostatic complementarity?
a charged group in the binding site interacts with a group of the opposite charge in the ligand
What is hydrogen bonding complementarity?
a hydrogen bond donor in the binding site interacts with a hydrogen bond acceptor in the ligand (or vice versa)
includes water-mediated interactions
What is hydrophobic complementarity?
hydrophobic groups in the binding site interacts with hydrophobic groups in the ligand to protect each other from interacting with water
How do you calculate the dissociation constant of a ligand-receptor interaction?
Kd = ( [P] [L] ) / [PL]
What is the dissociation constant?
Kd
the equilibrium constant for the dissociation reaction
What is the dissociation constant when half of the protein is bound to the ligand?
[P] = [PL]
and
Kd = [L]
Describe the relationship between Kd and affinity of a ligand for a protein.
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)
Describe the binding of oxygen in red blood cells.
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
What is the tense (T) state?
where hemoglobin has a low affinity for O2
What is the relaxed (R) state?
where hemoglobin has a high affinity for O2
Describe the cooperative binding of oxygen to hemoglobin.
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
Why is cooperative binding important for hemoglobin?
because it allows for hemoglobin to become completely saturated with oxygen in the lungs and release it in the tissues
What are allosteric effectors?
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
What molecules allosterically affect binding of oxygen to hemoglobin?
oxygen itself
CO2
protons
2,3-bisphosphoglycerate (2,3-BPG)
How does CO2 concentration affect the binding of O2?
- 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 - binding of CO2 to hemoglobin decreases its affinity for O2
How do protons affect the binding of O2 to hemoglobin?
lowering the pH decreases the affinity of hemoglobin for O2
more protons makes it acidic and a lower pH
What is the Bohr effect?
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)
How does 2,3-BPG affect the binding of O2 to hemoglobin?
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
What affects 2,3-BPG concentrations?
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)
How does 2,3-BPG interact differently with HbA and HbF?
does not bind strongly to HbF resulting in HbF having a higher affinity for oxygen
Why does HbF have a higher affinity for O2?
increases efficiency in transferring O2 from maternal red blood cells to fetal red blood cells
