Hemoglobin Flashcards
What is myoglobin for
oxygen binding protein
where is myoglobin found
in muscle
what is myoglobin made of in terms of helices
8 alpha helices
Hemoglobin is what type of protein
tetrameric
what groups does hemoglobin contain
4 heme groups
Are the amino acid residues of the alpha and beta subunits identical?
No, not identical
What is similar between the alpha and beta subunit
the 3D structure
difference between myoglobin and hemoglobin in terms of polypeptide chain
Myo has single chain but hemo has mutiple
does myo or heme bind easier to oxygen
Myo
difference between myoglobin and hemoglobin in terms of ‘meric’
Myo is monomeric and hemo is tetrameric
difference between myoglobin and hemoglobin in terms of how many oxygens can bind
Myo can bind one oxygen - monomer
hemo can bind 4 oxygens - tetramer
The quaternary structure of hemoglobin features strong interactions between what
unlike subunits
alpha1beta1 and alpha2beta2 interface involves how many residues and remains intact when what occurs
involves 30 residues
remains intact when the tetramer is disassembled with urea
alpha1beta2 and alpha2beta1 interface involves how many residues and interactions are mostly what
involves 19 residues
mostly hydrophobic although there are many hydrogen bonds
Mb and Hb fold into similar what
tertiary structures
The backbone of mb and hb consists of what
8 alpha helices separated by bends
side chains extend outward from the helices occupying what
nearly all the space between the folded loops
what residues arent found on the outer surface and which ones are found in the interior
polar residues found on outer surface
hydrophobic residues in the interior
The proline residues coincide with what
the loop regions
the heme group is located within a pocket lined with what
hydrophobic amino acid side chains
Heme is held in the hydrophobic pocket by coordinationof the iron with what
His93/F8
On the other side of the heme, the iron is coordinated with what
a water molecule (deoxy form) or an oxygen molecule (oxy form)
Another histidine, His64/HisE7 does what
helps hold the oxygen molecule in place
how does oxygen bind to myglobin
reversibly
For a monomeric protein such a myoglobin, the fraction of binding sites occupied a ligand is what
a hyperbolic function of ligand concentration
Binding of oxygen to hemoglobin undrgoes what
a structural change
what are the two major conformations of hemoglobin
R Relaxed and T Tense
O2 has a significantly higher affinity for what
Hemoglobin in R state
R state is also what
Oxyhemoglobin
T state is also what
deoxyhemoglobin
in the absence of o2 which state is more stable
T state
The binding of O2 to hemoglobin subunit in the T state triggers a change in conformation to what state?
R state
What happens in terms of structure during the transition between T and R state
when going from T to R, the alphabeta subunit slide past each other and rotate - narrowing of the pocket
What happens to the ion pairs that stabilise the T state when going to R state
ion pairs are broken and new ones are formed
what is the problem with having a protein with high affinity for o2 but is needed in 2 different places
A protein with high affinity for O2 in the lungs would not be able to release it in the tissue, and a protein with high affinity for O2 in the tissue would not bind much O2 in the lungs.
Different kPa’s
How does hemoglobin solve the problem of O2 binding in areas of different kPa
Undergoes transition from low affinity state (T state) and a high affinity state (R State)
Transition from two states resulted in hemoglobin having what shape
S shaped/ Sigmoid binding curve
High affinity state is what
R state
Which has the higher pKa? Tissues or Lungs
Lungs
the binding of o2 to individual subunits can alter what
affinity for o2 in the next subunit
why does the fourth o2 molecule binds easier to heme than the first one
heme already in R state and so binds with much higher affinity
why is binding of o2 to hemoglobin an example of cooperative allosteric binding
binding of one ligand affects the remaining sites.
O2 can be considered as both a ligand and a homotropic modulator. There is only one O2 binding site per subunit, so the allosteric effect gives rise to cooperativity mediated by conformational changes transmitted from one subunit to another by subunit-subunit interactions.
Why does hemoglobin function efficiently in oxygen transport
is a result of allosteric transition between high and low affinity states
Allosteric changes in heme can also be promoted by what
Allosteric effectors - Carbon dioxide and protoons
A decrease in pH lowers what for Hb
lowers the affinity for O2 binding
