CASPASE THE FRIENDLY GHOST Flashcards
What are caspases?
site specific cysteine proteases responsible for most of the changes seen in apoptosis
Where are they synthesised?
In the cell as inactive precursors -PROCASPASES
Describe the structure of a procaspase molecule
N-terminal pro-domain and large subunit/small subunit domains.
What is caspase activated by?
proteolytic cleavage of procaspase between p20 and p10 domains (between large and small domains)
What suggests the possibility of autocatalytic activation?
The fact that all the cleavage sites are at Asp
What is the caspase cascade used extensively for?
The activation of downstream caspases (3,6,7)
What does the cysteine in the active site do?
Cleaves aspartic acid peptide bonds within proteins
What kind of a degree of specificity is there?
HIGH BITCHES
What are folds, quaternary arrangements and catalytic mechanisms like for all the caspases?
THE SAME BITCHES
Describe caspase-3 dimer’s structure
Fold has large subunit and small subunit. Each heterodimer has 6beta strands forming a twisted beta sheet structure, 2alpha helices on one side, 3 other.
Describe caspase-8 dimer’s structure
2 heterotetramers.
Where is the recognition of the substrate occuring predominantly?
In the cleft formed by the loop regions of p18 and p12 subunits
How is the active site cysteine activated?
Polarised by a histidine residue.
What is the primary determinant for substrate spec?
P4 binding site
What is the P4 binding site like in C-1?
Large hydrophobic pocket, 4 large hydropho residues
