Zinc binding by fibrin facilitates proteolysis by a snake (puffadder) venom protease.

PAV protease is able to cleave between the crosslinked sites of the gamma-chain of fibrin and fibrin-derived D-dimer. The rate of digestion can be increased fourfold to tenfold by the addition of zinc ions. Although the PAV protease is a zinc-containing metalloenzyme, the enhanced rate of cleavage can be shown to be due to histidine-specific zinc binding by D-dimer. It is proposed that zinc ions cause a distortion of the inter-crosslink peptide chain, creating a novel protease-susceptible site. The physiologic relevance is uncertain due to the relatively low measured zinc binding constant Kd = 10(-3.88) M. Zinc binding could, nevertheless, create a useful fibrin-specific neoepitope for antibody recognition in vitro.