In this work we have described a novel component, termed here VaH3, as a potently hemorrhagic snake venom metalloproteinase (SVMP). Its proteolytic activity and overall stability depend on the presence of Zn2+ and Ca2+ ions. VaH3 is a dimeric composed of two identical monomers of 53.7 kDa. The complete amino acid sequence of VaH3 was determined by protein and cDNA sequencing. Each of the identical glycoprotein subunits comprise a metalloproteinase, a disintegrinlike domain and a cysteinerich domain, classifying VaH3 to the PIIIc class of SVMPs. It shows strong sequence similarity to vascular endothelial cell apoptosisinducing reprolysins. Antiammodytagin antibodies strongly crossreacted with VaH3 and completely neutralized its hemorrhagic activity in rat, despite the fact that these two hemorrhagic PIII SVMPs from V. a. ammodytes venom do not share a very high degree of amino acid sequence identity. VaH3 rapidly cleaved some basal membrane proteins, as well as some proteins involved in blood coagulation. These proteolytic activities most likely contribute to the hemorrhagic activity of VaH3. A threedimensional model of VaH3 was built to help explain structurefunction relationships in ADAM/ADAMTS, a family of proteins having significant therapeutic potential and substantial sequence similarity to VaH3.
COBISS.SI-ID: 26474535
The venom of Vipera ammodytes ammodytes causes different pathologic effects in man, the most pronounced being hemorrhage and local tissue damage. In this paper we described a systematic exploration of the hemostatic part of the venom. We detected venom components that degrade components of basal lamina and extra cellular matrix, proteolyze plasma proteins involved in blood coagulation and regulation of blood pressure, inhibit collagen-, adenosine diphosphate- and von Willebrand factor-dependent platelet aggregation/agglutination, activate factor IX, factor X and prothrombin, and inhibit prothrombinase complex formation. Nine venom proteins that affect hemostasis have been characterized in detail. Four of these have potential for medical exploitation.
COBISS.SI-ID: 27046439