Question

explain why trypsin and chymotrypsin break peptide bonds between different amino acids

Answer 1

Chymotrypsin has a binding cavity - a depression in the surface of the protein - which is very highly specific for bulky, non-polar aromatic rings on the side chains of tyrosine, tryptophan and phenylalanine. Specificity results from side chains making many favorable non-covalent interactions with the protein which are not made by side chains on different amino acids.

Trypsin, by contrast, has a binding site which forms many favorable non-covalent interactions with long side chains, specifically those found on lysine and arginine, except when they follow a proline which introduces a really rigid kink in the local conformation of the peptide.

Note that I said non-covalent bonds. That refers to the specificity and binding only: the actual hydrolysis reaction involves covalent bonds between various catalytic side chains in chymotrypsin and trypsin and the polypeptide which is being degraded. Even if chymotrypsin or trypsin did bind an inappropriate substrate, the enzyme wouldn't be able to catalyze a hydrolysis reaction because the side chains involved in catalysis wouldn't make the proper covalent interactions with the substrate.

Answer 2

Chymotrypsin and trypsin are serine protease. At the active site, there is a serine195, histidine57 and aspartate102. I can go into further details to how the mechanism works.

But in Chymotrypsin, it cleaves after amino acids (F,Y,W, L, and M) because it has an hydrophobic cleft that is able to fit large side chain amino acids.

In trypsin, there is a replacement of a serine residue at the bottom of the cleft to a Aspartic acid (negatively charged), which cleave after/attracts positively charged amino acids such as arginine (R) and lysine (K).