Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites.

Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure-function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation.

Purification, Partial Characterizations, and N-Terminal Amino Acid Sequence of a Procoagulant Protein FV-2 from Daboia Russelli Siamensis (Myanmar) Venom.

In this study, we purified and characterized the procoagulant protein FV-2 from Daboia russelli siamensis (Myanmar) venom using ion-exchange chromatography on CM-Sephadex C-50 and gel filtration on SuperdexTM G-75 column. The activation of factor X and prothrombin was determined, respectively, by specific chromogenic substrates. The fibrinogen-clotting activity, thermal stability, and pH stability were also determined. The N-treminal sequence was determined by the National Center of Biomedical Analysis of China. In the end, FV-2 was achieved with a molecular weight of 13,608.0 Da. It could activate factor X, but did not affect prothrombin or fibrinogen. The suitable pH was 6.5-7.5, and the suitable temperature ranged from 25 to 60°C. The N-terminal sequence was Asn-Phe-Phe-Gln-Phe-Ala-Glu-Met-Ile-Val-Lys-Met-Thr-Gly-Lys. Taken together, our studies suggest that FV-2 is a factor X-activating enzyme, which can activate factor X to factor Xa, but it has no effect on prothrombin and fibrinogen.

Purification, Biochemical Properties, and Activities of a Novel Factor X Activator (F V e-1 ) from Daboia Russelli Siamensis ( Myanmar ) Venom / 中山大学学报(医学科学版)

[Objective] To purify and characterize a novel factor X activator,Fve-1 from Daboia russelli siamensis (Myanmar) venom.[ Methods]F V e-1 was purified by ion-exchange chromatography and gel filtration.The hemostatic activity of F V e-1 was determined based on chromogenic substrates.The fibrinogen-clotting activity of F V e-1 was also determined.Thermal stability, pH stability,enzyme activity,and inhibition of F V e- 1 were determined by its remaining procoagulant activity.N-treminal sequence was determined by the method of automated Edman degradation.[ Results ]F V e-1 was achieved by chromatography with a molecular weight of 13,808 and an isoelectric point of 4.6. The hemostatic activity of 0.5 mg Fve-1 was equal to that of 1.5625 u thrombin or that of 54.93 ng RVV X. F V e-1 primarily activated F X, but did not affect on prothrombin and fibrinogen. The suitable pH and temperature range of F V e-1 was 6.5-7.5 and 25-60 ℃,respectively.The activity of F V e-1 was enhanced by Ca2+ and inhibited by EDTA and DTT.The N-terminal sequence of F V e-1 was NH2-N-L-Y-Q-F-G-E-M-I-N.[Conclusion] F V e-1 is a factor X-activating enzyme,which could activate FX to FX a,but have minimal effect on prothrombin and fibrinogen.