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Terms in this set (16)
What is chymotrypsin?
A protease secreted by the pancreas into the small intestine where it can hydrolyse dietary proteins.
What other protease are secreted by the pancreas?
Trypsin and elastase
What are zymogens?
The inactive form of proteases
What is the zymogen of chymotrypsin?
Why are proteases secreted as zymogens?
So that they do not hydrolyse and break down the pancreas.
How are proteases activated?
Activated by proteases already present in the small intestine which cleaves the zymogens.
Why can proteases be active in the small intestine?
Cells of the small intestine, enterocytes, are resistant to proteases.
What is the structure of chymotrypsinogen?
It is one polypeptide chain that is hydrolysed at 4 points to release 3 chains which are held together by intermolecular disulphide bonds.
How do chymotrypsin, trypsin and elastase differ?
Their substrate binding sites differ which are located immediately next to the peptide bond to be cleaved.q
What is a substrate binding pocket?
It is located next to the binding site and determines the binding specificity.
Describe the chymotrypsin binding pocket
Binding pocket is large and hydrophobic so is specific for aromatic side chains.
Describe the trypsin binding pocket
Has an Asp189 at the bottom of the pocket which is negatively charged and so specifically binds positively charged side chains such as Lysine and Arginine.
Describe the elastase binding pocket
Has several valine amino acids that block the bottom of the pocket and so is specific for amino acids with small side chains.
What forms the catalytic triad in chymotrypsin?
Asp102, His57 and Ser195
How is a charge relay system formed in chymotrypsin?
On binding of the substrate their is a change in conformation of the protein which facilitates the interactions between the catalytic triad.
Describe the catalytic mechanism of chymotrypsin
1. Binding of polypeptide chain to substrate binding pocket specifies what peptide bond will be cleaved.
2. Side chain binds into the binding pocket positioning peptide bond to be attacked.
3. Binding activates charge relay system allowing His57 to act as a base catalyst.
4. His57 acts as base catalyst and extracts a proton from the OH group Ser195 to form a reactive alkoxide.
5. Alkoxide on Ser195 attacks the peptide carbonyl group and covalent bond forms between carbon and Ser195, displacing the bond onto oxygen forming an unstable oxyanion (CO-)
6. Oxyanion briefly stabilised by the amino acid side chains that form an oxyanion hole.
7. Instability of oxyanion leads to it collapsing back on itself to reform CO.
8. Collapse of oxyanion requires displacement of one of the bonds linked to the carbon.
9. His57 acts as an acid catalyst and donates a proton to the amino group of the peptide.
10. Bond between carbon and amino group cleaved to get release of product 1.
11. Rest of protein still attached to Ser195 so H2O comes in to allow hydrolysis of remaining covalent bond.
12. Water deprotonated by His 57 acting as a base catalyst to generate a strongly nucleophilic hydroxide ion.
13. Oxygen attacks carbonyl, displacing bond onto oxygen forming another oxyanion.
14. Oxyanion stabilised by oxyanion hole.
15. Oxyanion collapsed back on itself, hydrolysing the bond between the oxygen of Ser195 and the carbonyl of the protein to release product 2.
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