Chymotrypsin

• OMIM: 118890
• UniProt: P17538
• MGI: 1913723

Chymotrypsin B is a digestive enzyme that is very similar to trypsin in its structure, but differs from it in particular through its milk clotting effect. The human chymotrypsin B and C belong to the serine proteases and are almost identical within the higher mammals. Several other chymotrypsins of marine life and insects were identified.

Chymotrypsin B is formed in the pancreas in the form of an inactive zymogen precursor ( chymotrypsinogen ). Cleavage of chymotrypsinogen into three sub- units is performed by trypsin in the small intestine, the assembly of the subunits to convert it to the active form ( chymotrypsin ).

Use in medicine

Is chymotrypsin as an active ingredient component of the enzyme preparations to be used in thrombophlebitis and other inflammations.

The determination of chymotrypsin in the stool can give access to different diseases of the pancreas, especially the exocrine pancreatic insufficiency. The determination of pancreatic elastase in the stool but is considered more sensitive.

Biochemistry

B preferably chymotrypsin cleaves at the peptide bonds whose carbonyl group of an aromatic amino acid (L- tyrosine, L- tryptophan or L-phenylalanine ), or L-leucine is derived. It thus belongs to the endopeptidases. Its mechanism of action of the catalytic triad of L- aspartate, L-histidine and L-serine, it is assigned to the serine proteases.

These three polar and highly conserved in serine proteases amino acids are also found in trypsin and in the elastase.

A likely enzymatic mechanism is shown in the illustrations. This binds to the polypeptide to be cleaved in chymotrypsin B, wherein the hydrophobic amino acid contained in the substrate ( in the figure is a phenylalanine, red) enters a specific binding pocket. This is also stabilized by a glycine ( Gly193 ) by hydrogen bonds.

In the first reaction step ( 1), a nucleophilic attack of the catalytic serine ( Ser195 ) to the peptide bond to be cleaved. The histidine -57 (His- 57) acts here as a base, since it removes a proton from Ser195. This creates a short-lived, a tetrahedral transition state with the subsequent cleavage of a bond to the rest of the substrate peptide is carried out (2). This leaves the enzyme. The remaining acyl- enzyme intermediate, however, is stable and can be isolated by means of substrate analogues.

By incorporation of water (step 3, blue) it reacts as nucleophile and attacks the carbonyl carbon of the intermediate to. His57 acts here as a base and accepts a proton of water on. It is again a tetrahedral transition state (4). This is short-lived (5). This sets the remaining polypeptide and regenerates as a result the Ser195. A new cycle can begin.