Pepsin

Exploring the Structure

Pepsin uses a pair of aspartate residues to perform the protein cleavage reaction. In an example of parallel evolution (where two organisms independently develop the same method for solving a problem), the mechanism is similar to that used by HIV protease, discussed in a previous Molecule of the Month. In the upper illustration, from PDB entry 5pep, the active site aspartates are seen as spacefilling spheres at the center of the deep active site groove, in white and red. In the lower illustration, three disulfide bridges are also shown. These crosslinks, formed between sulfur atoms (yellow) in cysteine amino acids, strengthen the protein chain.

These illustrations were created with RasMol. You can create similar illustrations by clicking on the PDB accession code and going to "View Structure." To highlight the active site aspartates, select residues numbered 32 and 215 in this structure file.