Myoglobin & Haemoglobin Flashcards
Why must oxygen be bound to proteins?
Very poorly soluble in the bloodstream
Structure of Myoglobin
- Predominantly helical
- Compact single polypeptide (153)
- Haem group contains porphyrin 9 with bound iron in ferrous state
What are the 6 co-ordination sites on Iron bound to?
4 to flat porphyrin ring system, 1 to proximal histidine on F-helix and other to oxygen
In deoxymyoglobin, the interaction of the iron with proximal histidine induces
A puckering of the porphyrin ring system
Binding site for oxygen on myoglobin
Deeply buried
How does oxygen enter the binding site on myoglobin?
Flexibility of molecule -> local breathing allows oxygen to move through local cavities in the protein
Mechanism for binding of oxygen on myoglobin
- Binds to 6th co-ordinating bond of haem bound iron
- Results in partial transfer of electron from ferrous ion to oxygen -> superoxide ion which isn’t stable
- Location of distal histidine on helix-E creates a H-bond to the bound oxygen + stabilizes it
- This prevents release of unreactive species
- H-bond pulls oxygen into plane of porphyrin ring
- Whole structure changes shape via movement of H-helix to tighten around bound oxygen molecule
Curve of Myoglobin
Hyperbolic
Curve of Haemoglobin
Sigmoidal
Myoglobin has a ____ affinity for oxygen at ___ pp
High, low
Structure of Haemoglobin
- Quaternary
- 2 alpha, 2 beta
- Bound haem containing iron in ferrous form
- Each subunit is capable of binding a molecule of oxygen
- Subunits sequentially dissimilar but structurally similar to myoglobin
- Key residues highly conserved and identical to myoglobin
Max Perutz
60’s + 70’s -> showed there are 2 major conformations of haemoglobin
Oxygen can bind to haemoglobin in both
T state or R state
Oxygen has a higher affinity in the
R state, stabilizing R state
In the T state
Predominant conformation of deoxyhaemoglobin. -> Binding of oxygen in T state triggers conformational change to R state, causing sub-units to change position relative to one another
Similarities between oxygen binding in myoglobin and haemoglobin
Binding of oxygen pulls iron into plane of porphyrin ring which changes position of helix F in sub-unit
Differences between oxygen binding in myoglobin and haemoglobin
Change in position of helix F in sub-unit in myoglobin acts only to stabilize structure but in haemoglobin this and other small changes causes sub-unit to rotate relative to other sub-units in structure so overall T to R conformation
Why is it important that haemoglobin binds to oxygen cooperatively?
Transition from low affinity T state to high affinity R state allows oxygen to be released effectively at tissues i.e. low partial pressures of oxygen
How is oxygen binding on haemoglobin co-operative?
- Oxygen binding on individual sub-units on haemoglobin can alter affinity for oxygen in adjacent sub-units
- First O2 that interacts with deoxyhaemoglobin binds weakly since sub-unit in T state
- Causes T-R transition and T-R transition occurs more readily in second sub-unit
- Oxygen binds readily to haem in final sub-unit b/c already in high affinity R state
What type of protein is haemoglobin?
Allosteric
Allosteric proteins
Proteins which have conformational changes that are induced by modulators making them more or less active forms
