Oxygen transport proteins
- myoglobin and hemoglobin are part of a large family of oxygen transport proteins
Ligand
a molecule that reversibly binds a protein
Globin family of proteins
- present in all branches of life (archae, bacteria, eukaryotes, prokaryotes)
- defined by the highly conserved globin fold - example of a structural motif
Why do we need proteins to transport O2?
- O2 cannot easily diffuse in mammals
- O2 is a diradical (reactive), leads to reactive oxygen series and damage biomolecules
What is the function of myoglobin?
- binds O2
- facilitates diffusion of O2 into muscle
What is the function of Hemoglobin?
- binds O2
- transports O2 through the body in blood
- picks up O2 from lungs and disperse to tissues
Structure of Myoglobin
- monomeric (1 chain, 1 subunit)
- 1 heme
Structure of Hemoglobin
- tetrameric (heterotrimer)
- 4 hemes
Prosthetic Group
non amino acid group that is bound to the protein
- many proteins contain prosthetic groups that support their function
What is the prosthetic group in myoglobin/ hemoglobin?
Heme group
What does a heme group do?
- A heme group is permanently bound to each globin domain and is responsible for O2 binding and the red color of Mb/Hb
When is a heme group added?
the heme group is added to Mb/Hb post-translationally and is responsible for binding O2
What does a heme group contain?
- a protoporphyrin ring
- Fe 2+ atom
What are the six bonds that “coordinate” iron?
-four nitrogens in the porphyrin ring, - one nitrogen in the proximal Histidine, and the O2
What is the ligand for myoglobin/hemoglobin?
oxygen
What binds iron?
The proximal histidine
What hydrogen bonds to the O2?
the distal histidine
Carbon monoxide poisoning
- CO bind to hemoglobin 40-times more tightly than O2
- O2 has a non linear bond while CO has a linear bond which is strongest allowing CO to outcompete O2
- Poisoning is a result of CO outcompeting O2
Equilibrium expression that describes the reversible binding of a protein (P) to a ligand (L)
P+L ⇌ PL
Ka=[PL]/[P][L]
Kd: Dissociation Constant
= 1/ Ka = [P][L]/[PL]
- smaller Kd= tighter binding
Fractional Saturation Y
- Y= [PL]/[P]+[PL]
= (bound active sites)/(total active sites) - Y= [L]/[L]+[Kd] ; form of a rectangular hyperbola
[L]=pO2 (partial pressure of O2)
What determines binding affinity?
chemical bonds and the intermolecular forces between ligand and its binding site
What are the pros/cons of high affinity binding?
- If binding is to high then it can’t unbind to complete its function
- we want reversible binding
- we need it to bind tight enough to do its job
Subunit Composition of Hemoglobin
-Hemoglobin tetramer: α2β2
-multiple globin genes
- fetal hemoglobin: α2γ2 (binds more tightly to oxygen)
