In this paper we report purification and characterization of a high molecular mass metalloproteinase with a fibrinogenolytic activity, termed VaF1, from the nose-horned viper (Vipera ammodytes ammodytes) venom. VaF1 slightly degraded collagen IV, nidogen and fibronectin, components of the ECM, in vitro and it would be expected to exert anti-coagulant action, due to its hydrolysis of fibrinogen, factor X, prothrombin and plasminogen, plasma proteins involved in blood coagulation. The complete amino acid sequence of the precursor of VaF1 was deduced by cloning and sequencing its cDNA. VaF1 is a typical P-IIIa subclass snake venom metalloproteinase. Interestingly, in standard experimental conditions VaF1 is not recognised by antiserum against the whole venom, so it can contribute to postserotherapy complications, such as ineffective blood coagulation, in the envenomed patient.
COBISS.SI-ID: 28236839
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
In this paper we described a novel high molecular mass hemorrhagin, VaH4 in the venom the nose-horned viper (Vipera ammodytes ammodytes). The isolated molecule is a covalent dimer of two homologous subunits, VaH4-A and VaH4-B. Complete structural characterization of A and partial characterization of B revealed that both belong to the P-III class of snake venom metalloproteinases (SVMPs). The hemorrhagic activity of this slightly acidic SVMP is ascribed to its hydrolysis of components of the ECM. VaH4 is also significant medically as we found it cytotoxic against cancer cells and due to its substantial sequence similarity to ADAM/ADAMTS family of physiologically very important human proteins of therapeutic potential.
COBISS.SI-ID: 27268903
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 diphosphateand von Willebrand factordependent 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
In this invited review we descride the most relevant haemostatically active proteins from snake venoms. Medical applications have already been found for some of these snake venom proteins. We describe those that have already been approved as drugs to treat haemostatic disorders or are being used to diagnose such health problems. No clinical applications, however, currently exist for the majority of snake venom proteins acting on haemostasis. We conclude with the most promising potential uses in this respect.
COBISS.SI-ID: 24433959