At first, pepsin is constructed with an extra 44 amino acids that serve in blocking the large active site groove so that the enzyme will not immediately begin digesting the cell's own protiens. Thus, pepsin starts off as an inactive proenzyme in the form of pepsinogen that is only activated after it is safely outside of the cell. Pepsinogen becomes activated only in very acidic environments, such as those inside the stomach, where it undergoes self-cleaving of those 44 amino acids that block the large active site to form active pepsin. Pepsin can also cleave the 44 amino acids off other pepsinogen enzymes so that they too can become active (Goodsell 2000).
The image to the left (in blue and yellow) is the structure of pepsinogen with the extra 44 amino acids (in yellow) that block its large active site. The image to the right (in white) is the structure of pepsin after the 44 amino acids have been cleaved from the active site. There are a total of 326 amino acid residues in pepsin (Dunn 2002).
The image above shows the overlap between pepsinogen and pepsin and the extra 44 amino acids in yellow.
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