Protein Function (myoglobin and hemoglobin) Flashcards
Ligand
anything reversibly bound by a protein
- can be any kind of molecule, including another protein
- when binded can cause conformational change
binding site
specific sit a ligand binds to
- complementary to the ligand in terms of shape, charge, etc.
- single protein may have many
What are the ligand of hemoglobin?
2,3 bisphosphoglycerate:
- regulates hemoglobin
- a lot of negative charge (a bunch of positive charge i the binding pocket)
Protein breathing
Lots of flexibility and changing by ligand bonding
Induced fit
Protein pushed towards a particular shape by the binding of a ligand
- change properties of proteins
What is the issue with oxygen delivery to cells?
- oxygen has low solubility in blood so it can’t do passive diffusion
- amino acids chains not well suited for reversible binding of oxygen
- transition metals are good for binding with oxygen but release free radicals
How do is the issue of the oxygen delivery/storage solved?
- specialized proteins are made
- heme group safely binds iron to oxygen
Myoglobin
monomeric protein that is used as a oxygen storage in peripheral tissue?
- Binds single oxygen (hugs)
- tertiary structure
- Have high affinity for oxygen (strong binding)
Hemoglobin
tetrameric protein found in red blood cells that transport oxygen from lungs to periphery
- hugs and releases oxygen
- goes back to lungs
- quaternary structure
- essentially 4 myoglobins together
Structure of Heme group
- Fe(II) is in the middle while four protoporphyrin rings surround it each presenting a N
- electron donating from N prevents the Fe(II) from turning into Fe (III)
- needs a specialized system to make these groups
Fe(II) seeks six interactions:
- four coming from heme group
- Fifth comes from a histidine (imidazole group)
- sixth is from oxygen
- another distal histidine binds onto oxygen for stabilization (transport oxygen)
How does carbon monoxide poisoning work?
- instead of oxygen binding to the heme group carbon monoxide does instead since it has a similar structure
- greater affinity
P50 value
amount of oxygen needed to half saturate a protein
Myoglobin - 3
Hemoglobin - 30
Myoglobin vs Hemoglobin curves
Myoglobin:
- more to the left (has higher affinity for oxygen)
- curve is constant instant binding (first oxygen makes it easier for the rest to bind)
Hemoglobin:
- more to the right (has lower affinity for oxygen
- s shaped curve (takes more energy for hemoglobin to be saturated)
What does it mean by Hemoglobin is an allosteric?
It has T (inactive) and R (active) forms (adopt different function)
- in rapid equilibrium
Difference between R and T form
T state:
- deoxy form (doesn’t have any oxygen bound)
** R state:**
- as more oxygens bind it does to R state
- lower affinity for oxygen
Why does Hemoglobin need to have an equal state of both high and low affinity?
- At high affinity it is not a very effective delivery system (holds onto oxygen)
- At low affinity it does not saturate itself fully at the lungs (not much to offload)
- equal with fully saturated and offload half of the amount
Allosteric modulators
Bind allosteric proteins at specific sites
- can be either activators or inhibitors
- activators stabilize the R state and inhibitors stabilize the T state
Homotrophic
Normal ligand and modulator are the same
Heterotrophic
Normal ligand and modulator are different from each other
describe how oxygen is a homotropic allosteric activator for hemoglobin
- each subunit of hemoglobin start out in the T state (no oxygen)
- as more oxygen is added not much is going to happen since it’s in the T state (low affinity)
- eventually an oxygen binds to a subunit (ligand), changing to an R state
- promote the other subunits to go to the R state even though they don’t have an oxygen bound
- saturated with oxygen very quickly
- serves as primary ligand for first subunit but allosteric modulators for the others
What kind of modulator is 2,3 bisphosphoglycerate?
Heterotropic allosteric inhibitor
- decreases hemoglobin’s affinity for oxygen
How does the binding site work for bonding 2,3 bisphosphoglycerate?
- BPG is a very negatively charged protein
- The binding site of histidines and lysines are going to be very positive
- electrostatic interaction
- favors T state
