[How and why is pepsin stable and active at pH 2?].

The HCl in the mammalian stomach is concentrated enough to digest the stomach itself and to cause denaturation of proteins. The paper summarize studies which explain why the gastric epithelium remains undamaged and gastric proteinase pepsin has the most stable and active structure at such extreme conditions. Pepsin is the first proteinase which starts protein proteolysis during the multistep process of protein digestion, and it splits mainly their hydrophobic cores unfolded in acidic media. Data on the disposition of the charged groups in the three-dimension structure of pepsin, which explain the extraordinary properties of the enzyme, are discussed.