Lecture 8 - Cooperativity and allostery Flashcards
If we have a protein with one binding site for a ligand, the number of ligands bound per site depends on
- Ligand concentration in solution
- Binding constant, K
The number of ligands bound per site is called the
fractional saturation (ϴ)
A binding curve for a ligand and a protein with more than one binding site is _______ shape.
sigmoidal
A binding curve for a ligand and a protein with one binding site is _______ shape.
hyperbolic
Cooperative binding
The binding of one ligand to one site increases its affinity to the next site
Cooperative binding is a property of _______ proteins
multisubunit
For cooperative binding, the first binding step corresponds to a(n) ______ in Gibbs energy
increase
Cooperativity is the key mechanism for
allosteric regulation
Allosteric regulation is
the regulation of an enzyme or protein by binding an effector molecule to a site other than the enzyme’s active site
Allosteric sites allow effectors to bind to the protein, resulting in a
conformational change
Allosteric activators are
effectors that enhance the protein’s activity
Allosteric inhibitors
effectors that decrease the protein’s activity
The approach to saturation is controlled only by the
binding constant K
Hemoglobin role
transport O2 from lungs to tissues
Myoglobin role
O2 storage protein
For Hill equation, n>1 is
positively cooperative binding
For Hill equations, n<1 is
negatively cooperative binding
For Hill equations, n=1 is
noncooperative binding
In positively cooperative binding, once the ligand molecule is bound to the enzyme, its
affinity for other ligand molecules increases
In negatively cooperative binding, once the ligand is bound to the enzyme, its
affinity for other ligand molecules decreases
In noncooperative binding, the affinity of the enzyme for a ligand molecule
is not dependent on whether or not other ligand molecules are already bound
The two models to describe how ligand binding at one site influences ligand-binding affinity at another identical site
- symmetry model
- sequential model
Oligomer
a polymer whose molecules consist of relatively few repeating units
In the symmetry model, protomers can exist in what states
T and R
In the symmetry model, the ligand can bind to
both the T and R states
In the symmetry model, the molecular symmetry of the protein must be
conserved during conformational changes
In the symmetry model, no oligomers contain both
T and R states
The ______ model allows for a more flexible interaction between a ligand and protein than the symmetry model does.
induced-fit
The sequential model of cooperativity is based on the
induced-fit model
The two states, T and R, stand for what?
tense (or taught), and relaxed
In the sequential model, when a subunit binds oxygen, that subunit changes from the
T state to the R state
In the sequential model, oligomers can contain
both T and R states
In the sequential model, the most likely states are
the totally empty and the fully bound states
In positive cooperativity, the binding of a ligand to one subunit
increases the ligand affinity of another subunit
In negative cooperativity, the binding of a ligand (inhibitor) to one subunit
decreases the ligand affinity of another subunit
The essence of the sequential model is that the protein’s ligand binding affinity
varies with the number of bound ligands
