Acid Base Catalysis (Lec4)

Question 1

Give a summary of the 6 proteins highlighted in this lecture

Answer 1

• aspartyl proteases - cysteine - serine - EQolysin - metalloproteases - threonine peptidases

Question 2

Give the role of Thr peptidases in the proteasome

Answer 2

Proteasome is small cylindrical shape (intracellular) has many sites for proteolytic cleavage (has 2 a and 2 b subunits) Thr peptidases exist within the B subunit eg B5 has chymotryptic like activity

Question 3

How do Thr peptidases cause proteolysis (give the initial steps)

Answer 3

• Thr O- nucleophile generated when Lys removes a H+ from the OH

Question 4

Give the name of the inhibitor that targets the proteasome and how it forms a covalent link with the enzyme

Answer 4

Bortezomib contains a B (linked to a dipeptide) that wants to be tetrahedrally coordinated to become B-

binds to the O- of Thr

Question 5

What is a carboxypeptidase and give an example of the type of metal found in this enzyme.

Answer 5

Carboxypeptidase - zinc exopeptidase that cleaves target towards the terminus of the polypeptide

Question 6

How is the Zn ion of a carboxypeptidase coordinated?

Answer 6

coordinated by a water molecule, 2 His and a Glu residue

Question 7

What residue does EQolysin use to activate water?

Answer 7

Glu

Question 8

Give the initial reaction of any reaction involving Cys proteases eg papain

Answer 8

His removes the H from Cys leaving an S- nucleophile