principles of the regulation of protein activity Flashcards
why is protein activity regulated?
protein activity needs to be regulated to control the activity of enzymes and so controls metabolic pathways, this ensures metabolic pathways are operating efficiently.
how is the biological activity of proteins regulated?
- allosteric binding by modulators
- reversible covalent modification
- proteolytic activation
- regulation through binding proteins
what is a modulator?
a modulator molecule is one which binds to the enzyme at an allosteric site.
binding of a modulator induces a conformational change in the enzyme which affects the shape of the active site and the affinity of the substrate.
modulators do not bind permanently, when their concentration falls, they are released from the allosteric sites.
what is a positive modulator?
a positive modulator binds to the allosteric site and increases the affinity of the enzyme for its substrate.
what is a negative modulator?
a negative modulator binds to a different allosteric site and reduces the affinity of the enzyme for its substrate.
what is homotrophic binding?
in homotrophic binding the modulators binding to the protein are the same.
what is heterotrophic binding?
in heterotrophic binding the modulators binding to the protein are different to each other.
haemoglobin
haemoglobin the oxygen transport protein is an example of an allosteric protein.
oxygen is transported in the blood from the lungs (where the partial pressure of oxygen (pO2) is relatively high) to the tissues (where the partial pressure of oxygen is much lower)
the homotrophic regulation of haemoglobin by its ligand oxygen increases its physiological oxygen-carrying capacity.
oxygen and haemoglobin
oxygen acts as a positive modulator for haemoglobin.
the binding and release of oxygen in haemoglobin shows co-operativity - changes in binding of oxygen at one subunit alters the affinity of the remaining subunits for oxygen.
initially there is a weak affinity for oxygen and the binding of the first oxygen molecule is slow. the binding of the first oxygen molecule induces a conformational change in the second haem subunit which increases affinity for the second oxygen molecule increasing speed of binding, this repeats for the third and fourth subunit.
what is covalent modification?
covalent modification of molecules is when covalent bonds are made or broken.
covalent modification changes an enzymes shape making the enzyme either active or inactive, so the concentration of active enzyme is changed, therefore the reaction rate is changed.
what is protein phosphorylation?
reversible phosphorylation is an important regulatory mechanism.
phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule through a condensation reaction.
reversible phosphorylation results in a conformational change in the structure, causing proteins to become activated or deactivated.
what enzymes are involved in phosphorylation?
enzymes called kinases and phosphatases are involved in phosphorylation.
kinases > phosphorylation (kind kinase)
phosphatase > dephosphorylation
which amino acid residues does phosphorylation occur on?
phosphorylation usually occurs on serine, threonine, and tyrosine due to the presence of a hydroxyl group causing them to be polar.
phosphorylation on serine is the most common.
how does phosphorylation occur on amino acid residues?
the phosphate gets added to the polar end of the R-group of the amino acid through a condensation reaction.
what is the consensus sequence recognised by protein kinase A?
arg-arg-X-ser-Z
or
arg-arg-X-thr-Z
where X is a small residue and Z is a large hydrophobic residue.
