Proteases Flashcards
What is a protease
A protease is an enzyme that forms proteolysis
It is also a protein that can be activated and processed by other proteases through proteolytic cascades
Proteases act bus hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain that forms the protein
Protein that breaks down proteins
Proteinase
Protease that breaks down peptides
Peptidase
How is protease activity regulated
Through the timely expression of proteases at the right place
Many proteases are expressed as zymogens , which are protein precursors which themselves need to be proteased to be active .
Natural protein inhibitors
What are zymogens
A zymogens is an inactive enzyme precursor. And a mechanism to control inappropriate proteolysis
Zymogens MOA
an inactivating polypeptide / propeptide stabilises the structure of the inactive protein. And masks the active site , preventing the binding of a substrate.
Thus is critical to long term bio stability of the enzyme and the protein is available immediately if needed eg clotting cascade
Activation of zymogens is through
Proteolytuc removal of the propeptide by another proteases or can be autocatalysis
This reveals the active site and converts the inactive zymogen into an active enzyme.
Sequential activation of protease zymogens allows the formation and strict regulation of a proteolytic cascade in which a signal, is passed through a Pathway
Advantages of zymogens
Rapid and efficient amplification of an organisms response to a physiological signal, therefore conserving energy
Drug development with zymogens
By targeting a Key protease hugh up in the cascade a protease inhibitor can switch off an entire pathway
What do the residues in the binding site of a protease do
Bind and orient substrates
What do the residues in the catalytic site do
Responsible for the chemical , hydrolytic cleavage step
How is an amino acid bonded
Peptide bonds that covalently link the carboxyl group of one amino acid with the amino group of another
What is a scissile bond
A covalent chemical bind tgat can be broken by an enzyme
How does proteolysis occur
P positions on the peptide correspond to complementary s positions (specificity pockets) on the protease active site
P s etc to left of scissile bond and p’ etc to right to yield two products
Example of non specific proteases
Digestive proteases such as pepsin which cleave a wide range of protein substrates into smaller peptide fragments for digestion and can cleave their substrates at multiple sites
Example of specific protease
Signalling pathways and blood clotting. These only cleave at very specific sequences
This increased specificity involves multiple specific interactions between amino acid residue on substrate (p) and the protease binding ‘specificity pockets’ (s)
