Snake metalloproteinase

Direct Fibrinolytics Alfimeprase is a recombinant tmncated form of fibrolase, a fibrinolytic zinc metalloproteinase isolated from the venom of the Southern copperhead snake. It degrades fibrin directly and achieves thrombolysis independent of plasmin formation. This may result in faster recanalization and a decreased risk of hemorrhagic conversion. The initial data on the safety and efficacy of alfimeprase in peripheral arterial occlusion disease appeared very promising, but recent communication from the sponsor revealed that the phase III trials of the drug in peripheral arterial disease and catheter obstruction (NAPA-2 and SONOMA-2) failed to meet their primary and key secondary endpoints of revascularization. A trial for I AT in acute stroke (CARNEROS-1) is planned to begin soon. 

Bode W, Gomis-Ruth FX, Stocker W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit idential zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the metzincins. FEBS Lett 1993 331 134-140. 

ADAM. A Disintesrin And MetalloProteinase family of proteins. Disintegrins, as the name implies, are proteins which interfere with interactions of cells with proteins in the extracellular matrix. An example are the inhibitors of the interaction of blood platelets with fibrinogen. Disintegrins are found in snake venom. Metalloproteinases are a family of proteases which need a bivalent cation for catalysis. MMP s are matrix metallo-proteases. They are associated with the extracellular matrix. 

Jarariiagin, a snake venom fi om Bothrops jararaca, contains a metalloproteinase that cleaves the p, subunit (GPIIa) of the receptor complex, resulting in an inhibition of platelet adhesion to collagen" as well as an inhibition of early platelet signalling events in response to collagen, as demonstrated in the loss of pp72(syk) phosphorylation. 

Grams, F., Huber, R., Kress, L.F., Moroder, L., and Bode, W. (1993). Activation of snake venom metalloproteinases by a cysteine switch-like mechanism. FEES Lett. 335 76-80. 

Jia, L.G., Shimokawa, K., Bjamason, J.B., andFox, J.W. (1996). Snake venom metalloproteinases Structure, function and relationship to the ADAMs family of proteins. Toxicon. 34 1269-1276. 

Kamiguti, A.S., Hay, C.R., and Zuzel, M. (1996). Inhibition of collagen-induced platelet aggregation as the result of cleavage of a P.-integrin by the snake venom metalloproteinase jararhagin. Biochem... 

Kini, R.M. and Evans, H.J. (1992). Structural domains in venom proteins Evidence that metalloproteinases and nonenzymatic platelet aggregation inhibitors (disintegrins) from snake venoms are derived by proteolysis from a common precursor. Toxicon. 50 1-29. 

Moura-da-Silva, A.M., Laing, G.D., Paine, M.J., Dennison, J.M., Politi, V., Crampton, J.M., and Theakston, R.D. (1996). Processing of pro-tumor necrosis factor-a by venom metalloproteinases A hypothesis explaining local tissue damage following snake bite. Eur. J. Immunol. 

Snake venoms, particularly those from North American pit vipers, contain direct-acting fibrinolytic proteinases (13). Fibrolase is the fibrinolytic enzyme from southern copperhead venom (14). Fibrolase is a non-glycosylated metalloproteinase with a molecular weight of 23,000 it contains one mole of zinc per mole of protein (14). The enzyme has an isoelectric point of approximately pH 6.8. The amino acid sequence of the enzyme has been determined... 

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