Disintegrin

Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Disintegrins are a family of small proteins (45–84 amino acids in length) from viper venoms that function as potent inhibitors of both platelet aggregation and integrin-dependent cell adhesion. Disintegrins work by countering the blood clotting steps, inhibiting the clumping of platelets. They interact with the beta-1 and -3 families of integrins receptors. Integrins are cell receptors involved in cell–cell and cell–extracellular matrix interactions, serving as the final common pathway leading to aggregation via formation of platelet–platelet bridges, which are essential in thrombosis and haemostasis. Disintegrins contain an RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequence motif that binds specifically to integrin IIb-IIIa receptors on the platelet surface, thereby blocking the binding of fibrinogen to the receptor–glycoprotein complex of activated platelets. Disintegrins act as receptor antagonists, inhibiting aggregation induced by ADP, thrombin, platelet-activating factor and collagen. The role of disintegrin in preventing blood coagulation renders it of medical interest, particularly with regard to its use as an anti-coagulant. Disintegrins from different snake species have been characterised: albolabrin, applagin, barbourin, batroxostatin, bitistatin, obtustatin, schistatin, echistatin, elegantin, eristicophin, flavoridin, halysin, kistrin, mojastin (Crotalus scutulatus), rubistatin (Crotalus ruber), tergeminin, salmosin, tzabcanin (Crotalus simus tzabcan) and triflavin. Disintegrins are split into 5 classes: small, medium, large, dimeric, and snake venom metalloproteinases. Small Disintegrins: 49-51 amino acids, 4 disulfide bondsMedium Disintegrins: 70 amino acids, 6 disulfide bondsLarge Disintegrins: 84 amino acids, 7 disulfide bondsDimeric Disintegrins: 67 amino acids, 4 intra-chain disulfide bondsSnake Venom Metalloproteinases: 100 amino acids, 8 disulfide bond Disintegrins evolved via gene duplication of an ancestral protein family, the ADAM family. Small, medium, large, and dimeric disintegrin family are found only in the family Viperidae, suggesting duplication and diversification about 12-20 million years ago. Snake venom metalloproteinases are found through the entire superfamily Colubroidea, suggesting that they evolved before Colubroidea diversified roughly 60 million years ago.