Download
1 / 37
370 likes | 375 Views
AH Biology: Unit 1 Proteomics and Protein Structure 3. Binding to Ligands. Think. How is protein production controlled? Why is it important that protein production is controlled? Why is protein structure important in relation to its function?. Binding to ligands.
E N D
AH Biology: Unit 1Proteomics and Protein Structure 3 Binding to Ligands
Think • How is protein production controlled? • Why is it important that protein production is controlled? • Why is protein structure important in relation to its function?
Binding to ligands • A ligand is a substance that can bind to a protein. • R groups not involved in protein folding can allow binding to these other molecules. • Binding sites will have complementary shape and chemistry to the ligand. • The ligand can either be a substrate or a molecule that affects the activity of the protein.
Nucleosomes • Nucleosomes animation • DNA replication animation
Transcription • Other proteins have binding sites that are specific to particular sequences of double-stranded DNA and when bound to can either stimulate or inhibit initiation of transcription. • lac Operon • Transcription animation
Binding changes the conformation of a protein • Enzymes and proteins are three-dimensional and have a specific shape or conformation. • As a ligand binds to a protein binding site, or a substrate binds to an enzyme’s active site, the conformation of the protein changes. • This change in conformation causes a functional change in the protein and may activate or deactivate it.
Induced fit • In enzymes, specificity between the active site and substrate is related to induced fit. • When the correct substrate starts to bind, a temporary change in shape of the active site occurs, increasing the binding and interaction with the substrate. • Induced fit
Allosteric enzymes • An allosteric enzyme is an enzyme that can have its activity altered by a ligand called a modulator. • In allosteric enzymes, modulators bind at secondary binding sites away from the active site. • The conformation of the enzyme changes and this alters the affinity of the active site for the substrate.
Modulators • Negative modulators reduce the enzyme’s affinity for the substrate. • Positive modulators increase enzyme affinity for the substrate.
Negative modulators • End product inhibition occurs when the final product of a cascade of enzyme reactions interacts with an allosteric site of the first enzyme in the cascade to inhibit it and thus the production of the end product. • This is an example of negative feedback. • End product inhibition animation
Competitive inhibition example 1 • Ethanol is metabolised in the body to acetaldehyde by oxidation with alcohol dehydrogenase, which is in turn further oxidised to acetic acid by aldehyde oxidase enzymes. • Normally, the second reaction is rapid so acetaldehyde does not accumulate in the body. • A drug called disulfiram (Antabuse) inhibits the aldehyde oxidase, which causes the accumulation of acetaldehyde with subsequent unpleasant side effects of nausea and vomiting. • This drug is sometimes used to help people overcome alcoholism.
Competitive inhibition example 2 • Methanol poisoning occurs because methanol is oxidised to formaldehyde and formic acid, which attack the optic nerve and cause blindness. • Ethanol is given as an antidote for methanol poisoning because ethanol competitively inhibits the oxidation of methanol. • Ethanol is oxidised in preference to methanol and consequently the oxidation of methanol is slowed down and the toxic by-products do not have a chance to accumulate. • The methanol is then excreted in the urine.
Competitive inhibition example 3 • Ethylene glycol, if ingested, can be poisonous. • Ethylene glycol is oxidised by the same enzymes used in the previous two examples. • Ethylene glycol → glycolaldehyde → glycolic acid. • Glycolic acid is toxic to the nervous system and kidneys. • Describe how ethanol can be used as an antidote.
Competitive inhibition • If the concentration of inhibitor is less than that of the substrate and the substrate has a higher affinity for the active site, is the enzyme inhibited a lot or a little? • If the concentration of inhibitor is more than that of the substrate is the enzyme inhibited a lot or a little? • If the enzyme is inhibited and we then increase the substrate concentration what happens to the initial rate of reaction?
Positive modulators • Positive modulators increase the enzyme affinity for the substrate by altering the shape of the active site so that it has a better fit for the substrate. • Positive modulation animation of a steroid on a GABAA receptor linked ion channel.
Enzyme kinetics questions • Enzyme kinetics questions.
Cooperativity in haemoglobin • Binding and release of oxygen in haemoglobin.
Cooperativity in hemoglobin • Deoxyhaemoglobin has a relatively low affinity for oxygen. • As one molecule of oxygen binds to one of the four haem groups in a hemoglobin molecule it increases the affinity of the remaining three haem groups to bind oxygen. • Conversely, oxyhaemoglobin increases its ability to loose oxygen as oxygen is released by each successive haem. • This creates the classic sigmoid shape of the oxygen dissociation curve.
Effects of temperature and pH • Low pH = low affinity. • High temperature = low affinity. • Exercise increases body temperature and produces CO2, acidifying the blood. • This has a corresponding effect on the oxyhaemoglobin dissociation curve.
Oxygen dissociation curve • Oxygen dissociation review in relation to a patient admitted to hospital. • What sort of conditions affect the ability of red blood cells to transport oxygen? • Under what conditions would haemoglobin struggle to bind oxygen?
Red blood cell disorders • Sickle cell anaemia • Thalassaemia
High-altitude conditions • High-altitude medicine • High-altitude effects: BBC Horizon, ‘How to Kill a Human Being’
Think • How is protein production controlled? • Why is it important that protein production is controlled? • Why is protein structure important in relation to its function?
