BIOL213 Lecture Notes - Lecture 14: Dissociation Constant, Atp Synthase, Reaction Rate Constant
Lecture 14 – Protein-ligand Binding
Protein function and ligand binding
• Proteins are dynamic molecules so change shape often, and their conformation is
important for their function.
• The function of many proteins involves interactions with other molecules
• In many cases this is a reversible interaction. The interacting molecule is called a
ligand
Ligand:
• A molecule that binds reversibly to a protein
• The region in the protein where the ligand binds is called the binding site
• Ligands bind via the same non covalent forces that dictate protein structure. This
allows the interactions to be transient (reversible).
• An enzyme bound to a substrate is an example of a protein-ligand interaction.
• Protein-ligand binding allows cells to respond to changes in the environment and
metabolic needs
• There are many different ligands, and they are very varied.
Eg. Peptide hormones, steroidal hormones, carbohydrates, lipids, cofactors,
vitamins, DNA, RNA, oxygen.
Protein-ligand interactions:
• When the protein is an enzyme, the ligand is called a substrate and ligand-binding
site is called the catalytic site or active site.
find more resources at oneclass.com
find more resources at oneclass.com
Lecture 14 – Protein-ligand Binding
• Ka represents the association rate —> how quickly P and L come together. Kd is
the dissociation rate —> how quickly they go back to their individual molecules.
• The affinity of the protein-ligand interaction is described by:
-the association rate constant —> Ka or
-the dissociation rate constant —> Kd (most common)
• Kd is expressed in molar units. A lower Kd value corresponds to a higher affinity
of the ligand for the protein as it is less likely to dissociate so wants to stay bound
to the protein.
(The smaller the Kd, the higher the affinity)
• The Kd of a protein-ligand interaction typically rages from 10^-15 (very high
affinity) to 10^-5 (low affinity)
Binding sites and specificity:
• Proteins typically have high specificity. Specificity is attribute to the 3D structure
of the proteins binding site - the region formed from the folding of the
polypeptide chains.
• High specificity can be explained by the complementarity of the binding site and
the ligand.
• Complementarity is described in terms of:
-size
-shape
-charge
-hydrophobic/hydrophilic character
• A protein may have separate binding sites for several different ligands. This
is required in order to form large protein complexes /molecular machines eg.
ATP synthase. Different subunits of the protein interact with different ligand.
• Conformational changes often occur upon ligand binding —> this adaptation
is called the induced fit model. Induced fit allows for a loose interaction in the
beginning, but tighter binding once the interaction continues. Both the ligand and
find more resources at oneclass.com
find more resources at oneclass.com
Lecture 14 – Protein-ligand Binding
the protein can change their conformations - neither molecules
are ‘stiff’ structures.
Protein-ligand binding:
1. Binding pocket or cleft which is the right shape for a ligand (due to the protein
tertiary structure)
2. Specific interactions between a ligand and amino acid side chains of the protein (ie
non-covalent interactions)
Actual interactions are occurring which are attaching the ligand to the protein.
3. Interaction with a prosthetic group. A prosthetic group is a non-amino acid
containing group which is covalently attached to the protein - third party. An
example of this is type of interaction is the binding between oxygen and the
heme prothetic group in haemoglobin.
Prosthetic groups:
• A compound permanently associated with a protein that contributes to the
function of the protein.
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Protein function and ligand binding: proteins are dynamic molecules so change shape often, and their conformation is important for their function, the function of many proteins involves interactions with other molecules. In many cases this is a reversible interaction. Ligand: a molecule that binds reversibly to a protein, the region in the protein where the ligand binds is called the binding site, ligands bind via the same non covalent forces that dictate protein structure. Peptide hormones, steroidal hormones, carbohydrates, lipids, cofactors, vitamins, dna, rna, oxygen. Protein-ligand interactions: when the protein is an enzyme, the ligand is called a substrate and ligand-binding site is called the catalytic site or active site. Lecture 14 protein-ligand binding: ka represents the association rate > how quickly p and l come together. Kd is the dissociation rate > how quickly they go back to their individual molecules: the affinity of the protein-ligand interaction is described by:
