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.
Purves
L R
LR
Department of Chemical Pathology, Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
Naidoo
D P
DP
D000595:Amino Acid Sequence; D010450:Endopeptidases / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D014757:Viper Venoms / Q000201:enzymology*; D015032:Zinc / Q000378:metabolism*
D005338:Fibrin Fibrinogen Degradation Products; D014757:Viper Venoms; C036309:fibrin fragment D; D005337:Fibrin; D010450:Endopeptidases; D015032:Zinc