What is the Structure of Chymotrypsin?

Chymotrypsin

Chymotrypsin is a proteolytic enzyme which hydrolyses protein. It is synthesised in pancreas and secreted in duodenum through pancreatic duct. As the food passes from stomach to duodenum, it is enacted by chymotrypsin. Duodenum is the site of enzyme action. Chymotrypsin cleaves peptide bonds near aromatic amino acids.

Structure of Chymotrypsin – Amino acid Composition:

Chymotrypsin consists of a linear three polypeptide chains A, B and C which are linked by disulfide bonds. It consists of a total of 245 amino acid residues which attains a globular form after folding.

Some of the important amino acid residues are His (histidine at position 57) and Asp (aspartate at position 102) on chain B, Ser (serine at position 195) on chain C.

After correct folding these three important amino acids (His, Asp and Ser) are brought closer in a space. Close up of active sites results in activation of the enzyme. The negatively charged Asp partially takes hydrogen from His.

Thus a hydrogen bond between closely placed Asp and His is formed. In turn His attracts a hydrogen ion from the adjacent Ser hydroxyl (-OH) group and compensates the partial loss of hydrogen ion which it donated to Asp.

Consequently the negatively charged Asp causes a partial negative charge on Ser through His residue. This ‘charge relay system’ works in a specific order. These three amino acids are often called ‘catalytic triad’.

Chymotrypsin is specific to aromatic residues. A large space created in enzyme shape acts as specific site of chymotrypsin. Bulky aromatic hydrophobic amino acid residues bind to hydrophobic residues lining in the larger space of enzyme shape.

The susceptible peptide bonds come closer due to such binding which attack Ser residue. When substrate binding site is blocked, the enzyme becomes inactive.

Regulation of Chymotrypsin Activity:

Zymogen (an inactive precursor) undergoes proteolytic cleavage to form the active enzyme. Initially chymotrypsin is synthesised as chymotrypsinogen (inactive form). It is cleaved by trypsin which undergoes conformational changes. Consequently, active sites of the enzyme are exposed which is called as alpha-chymotrypsin (active form).