Lectures 7-8 Hb Flashcards
(40 cards)
primary structure of haemoglobin
around 150 amino acid-long primary sequence
whats the secondary hemoglobin structures
8 alpha helices, A-H.
whats the tertiary structure of haemoglobin
a globin fold with a hydrophobic pocket
what the quatenary structure of haemoglobin
4 monomeric units interacting to make the heteromeric quaternary structure.
what does the Haem group bind to
His F8
describe the structure of the haem group
a central Fe2+ ion bound to His F8 as well as 4 N pyrrole rings, leaving the one binding site for O2.
what other amino acid is important in O2 binding to haem and explain
the His E7. His E7 distorts the binding of the O2 to the Fe2+, This reduces the binding affinity of oxygen to myoglobin, making it easier to
release oxygen to the muscle cell. reducing the binding affinity through steric hindrance.
what is allosteric hindrance
hindrance of binding but not at the active site of the protein
what is the shape of the myoglobin curve
it is hyperbolic
what does the hyperbolic curve shape of myoglobin mean
Myoglobin is saturated with O2 at low
pO2 only releasing O2
to muscle cells
when the cellular pO2
is very low.
This is shown in a ‘hyperbolic’ curve.
This suits its function as a “back-up”
store of O2 in muscle cells.
what binds oxygen more tightly, the myoglobin or haemoglobin
myoglobin
how are the 4 globin subunits of haemoglobin joint together
via non covalent association bonds
describe T state
tense state and has low affinity for oxygen
describe R state
relaxed state and has high O2 affinity
describe the concerted model for Haemoglobin
Subunits can be in a low-activity,
tense (T) or high-activity, relaxed
(R) conformation.
* All subunits must be in the same
state (either T or R).
Binding each successive substrate
(S) shifts equilibrium in favour of R.
in the concerted model, what do inhibitors and activators do
inhibitors stabilise the T form, activators stabilise the R form
whats the sequential model
One substrate binding induces a T → R conformational
change in only one subunit.
* This conformational change influences the neighbouring
subunits (i.e. cooperativity), changing their affinity for substrate. Many conformations are possible, like 2T and 2R at the same time
what are the haem shapes in deoxy and oxy haemoglobin
in deoxyhaemoglobin the shape is dish shaped and oxyhaemoglobin is more flat
what flattens the haem group
the binding of O2 pulls iron ion into the plane of the haem
what happens when haem binds O2 in terms of shape
the haem group flattens, this pulls His F8 toward the haem binding site, which then causes a conformational change in helix F, which changes C. which then causes conformational changes and cooperativity in the other helices.
T/F, T state means deoxthaemoglobin
F
are the T state and R state and the binding molecules specific to haemoglobin
no, they apply to all multimeric proteins.
describe the conformational changes of haemoglobin binding
The change of position is in helix F, this changes angle between E and F. in Deoxy its more open, in oxy is closed. The binding moves FG in a fair bit.
As the F helix moves the FG loop moves upwards relative to the C helix.
BPG is a what? and what is its charge
its an allosteric inhibitor and it has -5 charge
