Question

Describe how the specificity pockets work- to determine the specificity of proteolytic cleavage at the active site of the serine-proteases. Discuss specific examples.

Answer 1

The serine proteases includes trypsin and chymotrypsin.These enzymes possess a hydrophobic pocket where the substrate binds and is known as primary substrate binding pocket or the S1 binding pocket.The S1 binding pocket in trypsin and chymotrypsin are found to be identical in primary sequences and the tertiary backbone structures but there occurs an important difference in the 189 residue.The 189 residue lies at the bottom of the S1 binding pocket and determines the specificity of proteolytic cleavage because the 189 residue is a negatively charged aspartate in trypsin while it is a polar serine in chymotrypsin.For example:The aspartate residue in the Asp 189 position located in the catalytic pocket (S1) of trypsin attracts and stabilizes the positively charged lysine and arginine and is thus responsible for the specificity of the enzyme.