Proteases 1 Flashcards
What are the defining features of a protease?
It is an enzyme that conducts proteolysis through hydrolysing peptide bonds to begin protein catabolism
What different roles do proteases play within the organism?
Protein turnover digestion activation of inactive preproteins signal transduction development coagulation complement activation apoptosis
How do proteases aid hydrolysis?
Bring substrates together to facilitate its reaction faster than the rate at which it would normally occur
This requires a surface or groove which fits the substrate, one or more suitable amino acids to activate the water molecule so it attacks the peptide bond
What is the catalytic mechanism in a serine protease?
Uses a catalytic triad of serine, aspartic acid and histidine which has a nitrogen which is made electronegative by the proximity to the aspartic acid
The OH group of serine attacks the carbonyl carbon
The nitrogen on histidine accepts a hydrogen from the serine OH group
Electrons from the double bond move up to bind the serine oxygen forming a tetrahedral intermediate
The peptide bond is broken
Electrons from this bond attack the hydrogen on the histidine and dislodge it
Electrons that left the double bonded carbonyl oxygen returns to recreate the bind forming an acyl-enzyme intermediate
Half of the cleaved polypeptide chain is now free to leave
Water takes the place of the removed half and electrons from the double bond move towards the oxygen to make it negative
The Nitrogen on histidine accepts one hydrogen from water and the OH of water bonds with the carbonyl carbon
The bond between serine oxygen and the peptide carbon attacks new hydrogen on histidine
Active site is regenerated and the carbonyl carbon reforms allowing the other half of the peptide to leave
What is the difference between a catalytic dyad and a catalytic triad?
A catalytic dyad has two active amino acid residues in its active site while a triad has three
What are the catalytic types of proteases?
Serine proteases, Cystine proteases, Aspartic proteases, metalloproteases, threonine proteases, glutamate proteases, asparagine peptide lysates
Name comes from the amino acid in the active site which acts as the nucleophile
Why is it necessary to control proteases?
Many proteases are non-selective and will cleave proteins that are not supposed to be degraded therefore the action of proteases must be regulated
How are the actions of proteases regulated?
Proteases are only present in certain locations
Often made as an inactive zymogen which needs activation
Can also be regulated by inhibitors
Using endo/exo peptidases
as exopeptidases will cleave only the free ends of proteins and endopeptidases will recognise specific sites within the primary structure and only cleave at those
What is unique about asparagine peptide lyases?
They cleave themselves using an asparagine residue as a nucleophile and does not involve hydrolysis
