Lecture 7 - Ligand binding Flashcards
Communication in the cell or between cells is ultimately achieved through
binding reactions in which a ligand binds to a macromolecule
Typically the ligand is a
small organic molecule or a metal ion that binds to a protein
The majority of interactions in biochemical systems begin with
binding of a ligand to a protein
In pharmacology, binding of a _____ to a _____ is one of the most common and important questions envisioned
drug; target
Biochemists express ligand affinities in terms of
dissociation constant (Kd)
Kd =
1/K
Kd is expressed in units of
concentration (M)
Binding constants (K) in biochemical reactions vary by
orders of magnitude
Enzyme-substrate interactions typically have Kd values from
0.1 uM to 1 mM
Receptor-ligand interactions typically have Kd values from
0.1 nM to 10uM
DNA-protein interactions typically have Kd values from
1 pM to 10 nM
The smaller the Kd, the
stronger the protein-ligand interaction
One of the strongest interactions known in a biochemical system is between
biotin and streptavidin
The binding curve is the ______ plotted against the _______
specific binding; free ligand concentration
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)
The approach to saturation is controlled only by the
binding constant, K
Kd represents the concentration of the ligand at which the protein is
half saturated
The binding constant (K) represents the ________ of the ligand for its binding site on the protein
intrinsic affinity
Antagonist
A substance that interferes with or inhibits the physiological action of another
Proton pump inhibitors (PPIs) inhibit
the H+/K+ ATPase pump that transports protons across membranes
Ligands can be ______ or ______
agonists; antagonists
Four different types of ligands
- Full agonist
- Partial agonist
- Antagonist
- Inverse agonist
Full agonists result in
a 100% response
Partial agonists cannot
achieve maximal response
The EC50 for a partial agonist is the
ligand concentration that results in 50% of the partial agonists full response
Full and partial agonists often bind to
the same binding site on a receptor
Antagonists bind to a receptor and cause
no response
An antagonist can be used to
block the binding of an agonist
As the concentration of the antagonist increases, the response of the agonist
decreases
An antagonist drug can be used to decrease the response of
a receptor
GPCR stands for
G protein coupled receptors
Serotonin receptors are GPCRs that
mediate both excitatory and inhibitory neurotransmission
Antagonists have different ______ for their receptor targets
potencies
IC50 means
half maximal inhibitory concentration
Constitutive receptors can
cause a response without a ligand being bound
An inverse agonist decreases the
constitutive receptor response to 0%
The inverse agonist has the capability to completely
shut down a receptor
The difference between an antagonist and an inverse agonist is that an antagonist results in
no response
