The Pepsin molecule - rotatable in 3 dimensions

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Pepsin is a protease (protein-digesting enzyme), which is active in the stomach.

The porcine pepsin molecule displayed here consists of 327 amino acid residues - 2797 atoms, ignoring hydrogen atoms, but this also includes oxygens from 375 water molecules!

The molecule has a deep cleft, the bottom of which contains the active site. This contains a pair of aspartate residues on either side of the cleft which break peptide bonds in proteins by the addition of water: -H to one side and -OH to the other. It is said that pepsin will preferentially break peptide bonds next to aromatic amino acids such as phenylalanine and tyrosine, but not next to valine, alanine or glycine. It does not therefore necessarily break down proteins into individual amino acids.

Pepsin is secreted as an inactive precursor pepsinogen.

Primary structure
Label /Unlabel amino acid residues

Secondary structure
Cartoon format - α helices red, β sheets gold

Active site
Aspartate residues 32, 215 in active site
Water in active site
Glycine residue 76 in flap above active site


There are several aspartyl protease enzymes with a broadly similar structure to mammalian pepsin, not all of which are strictly digestive in function:
  • chymosin (rennin) - the active ingredient of rennet, used in cheesemaking
  • cathepsins - a number of proteases found in lysosomes within cells and active at low pH
  • plasmepsins - a number of proteases produced by the malarial parasite Plasmodium . By breaking down haemoglobin, they are an important cause of symptoms in malaria sufferers and a potential target for antimalarial drugs.
  • HIV-1 Protease is a protease that is essential for the life-cycle of the HIV virus. Inhibition of this protease prevents maturation of HIV particles. Many drugs have been developed, so-called protease inhibitors, that target this enzyme

Web references


Pepsin - RCSB Protein data bank Molecule of the Month

Analysis of crystal structures of aspartic proteinases: On the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes Natalia S. Andreeva and Lev D. Rumsh

The pepsin residue glycine-76 contributes to active-site loop flexibility and participates in catalysis. Okoniewska M, Tanaka T, Yada RY.

Pepsin From Wikipedia, the free encyclopedia



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