Lecture 13: ACTIVATION AND INHIBITION OF PROTEINS (PART 1) Flashcards
What is the first common step in activation and inhibition of proteins?
Chemical substance travels from its source
What happens after the chemical substance travels from its source?
Chemical substance interacts with the target protein- binding/reception
What is reception?
When the protein receives the substance
What happens after the chemical substance interacts with the target protein- binding/reception?
The binding event effects the protein to either activate or inhibit it
What happens after the binding event effects the protein to either activate or inhibit it?
Functional consequences that change the cellular response
How does the activation and inhibition relate to HIV protease?
Saquinavir binds to HIV and inhibits any further action
What are receptors?
A cellular protein (or assembly of proteins) that control chemical signalling between and within cells
How many individual receptor proteins are there?
About 1000
What do receptors control?
Many important physiological processes, including sight, smell and taste
What are receptors the cellular targets for?
Many drugs and some toxins
What do one third of drugs do?
Activate or inhibit receptors
How do enzymes and receptors compare in binding sites?
Enzymes typically have one active site and receptors can have several binding sites
How do enzymes and receptors compare in what they bind?
Enzymes bind substrates and receptors ind ligands
How do enzymes and receptors compare in what they do to what binds?
Enzymes change substrate to product and receptors release the ligand unchanged
How do enzymes and receptors compare in where they are found?
They can both be found membrane bound or free in the cytosol
What can be don’t with both enzymes and receptors?
They can be activated, inhibited or used as drug targets
What are the main classes of receptors?
Ligand-gated ion channels, G protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK)
What is different between the three receptor classes?
Their structure which is important to their function
What is the same between the three receptor classes?
They have the same overall steps of activation and inhibition but the exact details differ
What is a ligand?
The general term given ti a chemical substance that specifically binds to a receptor
What may ligands be?
Diverse in chemical structure, ranging from small molecules to large peptides and even proteins
What are the types of ligands?
Endogenous and exogenous
What are endogenous ligands?
Ligands produced in the body
What are examples of exogenous ligands?
Drugs and toxins
What do all ligands do?
Make chemical contacts with their specific receptors
Where are most receptors found?
On the outer cell membrane, where they act as sensors of the extracellular environment
What does the ligand not usually have to do?
Pass through the membrane
What is the receptor known as?
The gate keeper of cellular activity, controlling it from the cell surface
How can intracellular responses to extracellular signals be produced?
By a membrane receptor being activated (ligand binding)
What is there between ligands and receptors?
Specificity
When will activation and inhibition happen?
only when the ligand receptor pairing is correct
What does the size and shape of the ligand match?
The corresponding receptor ‘binding pocket’ allowing enough chemical interactions for binding to occur
What happens if the ligand doesn’t match?
There will be no binding to the receptor
What is the mechanism for binding to receptor proteins used for?
To make drugs that bind only to certain receptor targets
What do medicinal chemists often do?
Often start with the chemical structure of an endogenous ligand, making new molecules from this to produce safe and effective medicines
What is an example of a medicine made by modifying the structure of an endogenous ligand?
Adrenaline (small molecule, endogenous ligand) is modified to form salbutamol (ventolin) which is an asthma drug
What can salbutamol do?
Activate the same receptor as adrenaline and mimic its effects to cause bronchodilator because both ligands can make similar chemical contacts with the receptor
What is an agonist?
A chemical substance (ligand) that binds to a receptor and activates it (may be endogenous or exogenous)
What happens first in activation of a receptor?
The agonist binds
What happens after the agonist binds?
The receptor undergoes a conformational (Shape) change to become activated - different ligands can cause different shape changes
What happens after the receptor is activated?
Active receptor starts a chain of events where messages are passed on through the cell via a process called signal transduction until there is a cellular response
What do different receptors use?
Different types of relay molecules to pass on the message
What is an antagonist?
A chemical substance (ligand) that binds to a receptor and prevents activation by an agonist (mainly exogenous)
What happens first in receptor inhibition?
Antagonist binds and blocks agonist binding
What happens after the antagonist binds and blocks agonist binding?
Receptor remains inactive
What happens after the receptor is inactivated?
Signal transduction does not occur so there is no cellular response
What does adrenaline do?
Acts as an agonist to activate the beta-adrenergic receptor (a GPCR). Signal transduction»_space;> Bronchodilation (cellular response)
What does insulin do?
Acts as an agonist to activate the insulin receptor (a RTK). Signal transduction»_space;> Glucose uptake (cellular response)
