Structure of astacin and the discovery of metzincins

The X-ray crystal structure of astacin from the freshwater crayfish Astacus astacus published in 1992 was the second structural prototype of a zinc metalloendopeptidase solved after thermolysin from Bacillus thermoproteolyticus 20 years earlier. Astacin became the founding member of a clan of metalloendopeptidases, for which Wolfram Bode coined the designation ‘metzincins’. This review recapitulates the discovery of the metzincin clan, which includes the astacins, MMPs (matrix metalloproteinases), serralysins and adamalysins/ADAMs (A disintegrin and metalloproteinase enzymes). Currently, over a dozen subclans (families) have been assigned including the pappalysins, leishmanolysins, snapalysins, igalysins, helicolysins, and toxylysins.