Amino acid sequence of a Crotalus atrox venom metalloproteinase which cleaves type IV collagen and gelatin

Abstract

The hemorrhagic toxin Ht-d from venom of the Western diamondback rattlesnake is a metalloproteinase with a molecular weight of 23,234. Peptides were obtained from enzymatic and chemical digestions, separated by reverse-phase chromatography, and sequenced in a gas-phase sequenator. The sequence showed a putative zinc binding site similar to that of thermolysin and other metalloproteinases but no overall significant similarity to the sequences of other metalloproteinases and may represent a new subfamily of metalloproteinases. Ht-d was shown to degrade type IV collagen and gelatin types I, III, and V but not interstitial collagens. The digestion of type IV collagen and other basement membrane proteins may allow this proteinase to disrupt capillary membranes causing hemorrhage in surrounding tissues.