Homo sapiens (human)
Proteases fulfill many important functions in the body cutting up other proteins. They usually have a deep cleft into which the sidechains of another protein can fit to line up the particular peptide bond that should be cut. Two particularly well studied kinds are the serine and the cysteine (or thiol) proteases. They are called so because the most important residue active in cutting the peptide bond is either a serine or cysteine. This residue together with a histidine and an aspartic acid forms a so called catalytic triad or charge-relay system which helps through relocation of proton charge to break the peptide bond. Trypsin belongs to one of two unrelated subfamilies of serine proteases, the trypsin family. The other family is called subtilisin family, with similar function but different overall structure. The mammalian serine protease are all members of the trypsin family, prokaryotic proteases often members of the subtilisin family. Being able to directly and indirectly influence many cellular processes, proteases are important targets for drug development.
The structure here, of human trypsin, shows the result of inhibition of the protease with diisopropyl-phosphofluoridate (DFP). This is a very potent inhibitor for serine protease, because the inhibitor forms a covalent bond with the serine in the active site. The results is complete and irreversible inhibition. A curious side effect of addition of DFP in this particular structure is the phosphorylation of an unrelated group, the sidechain of a tyrosine residue, with a phosphate attached to the hydroxyl group of the sidechain.
Protein Data Bank (PDB)
author: Arno Paehler