1ST STRUCTURE OF A SNAKE-VENOM METALLOPROTEINASE - A PROTOTYPE FOR MATRIX METALLOPROTEINASES COLLAGENASES

Adamalysin II, a 24 kDa zinc endopeptidase from the snake venom of Cro talus adamanteus, is a member of a large family of metalloproteinases isolated as small proteinases or proteolytic domains of mosaic haemorr hagic proteins from various snake venoms. Homologous domains have rece ntly been detected in multimodular mammalian reproductive tract protei ns. The 2.0 angstrom crystal structure of adamalysin II reveals an ell ipsoidal molecule with a shallow active-site cleft separating a relati vely irregularly folded subdomain from the calcium-binding main molecu lar body composed of a five-stranded beta-sheet and four alpha-helices . The folding of the peptide fragment containing the zinc-binding moti f HExxHxxGxxH bears only a distant resemblance to thermolysin, but is identical to that found in astacin, with the three histidines and a wa ter molecule (linked to the glutamic acid) likewise constituting the z inc ligand; adamalysin II lacks a fifth (tyrosine) zinc ligand, howeve r, leaving its zinc ion tetrahedrally co-ordinated. Furthermore, adama lysin II and astacin share an identical active-site basement formed by a common Met-turn. Due to their virtually identical active-site envir onment and similar folding topology, the snake venom metalloproteinase s (hitherto called adamalysins) and the astacins (and presumably also the matrix metalloproteinases/mammalian collagenases and the Serratia proteinase-like large bacterial proteinases) might be grouped into a c ommon superfamily with distinct differences from the thermolysin famil y.