Question

(a) Chymotrypsinogen is inactive form of enzyme chymotrypsin. Which molecular alteration converts it into active form?

(b) The catalytic triad in chymotrypsin leads to a charge relay system. Justify.

Answer 1

(a) In chymotrypsinogen, the substrate binding site is blocked and hence the enzyme is inactive. In-situ activation of trypsin involves a proteolytic cut in chymotrypsinogen which results in a conformational change, exposing the substrate binding pocket.

(b) Asp 102, His 57 and Ser 195 lie in this order forming a charge relay;

The negatively charged aspartate carboxylate residue pulls the Ser –OH proton through His, leaving it with a negative charge Ser195 becomes acidic due to the unique constellation of the three amino acid residues because the protein has folded uniquely in space.