Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The crude venom of many elapid snakes appeared to contain proteins that activated blood coagulation factor V. The factor V activator present in the venom of Naja naja oxiana was purified to homogeneity by chromatography on a mono-S column. The activator was a single chain protein with an apparent mol. wt of 48,000, as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and by gel permeation chromatography on Sephacryl S200. Activation of bovine factor V by the purified venom activator was accompanied by proteolytic cleavage of factor V and resulted in the formation of two major polypeptide chains with mol. wts of about 90,000 and 77,000. The final product obtained was compared with thrombin-activated factor V for its ability to function as cofactor in factor Xa-catalysed prothrombin activation in the presence of negatively charged phospholipid vesicles (5 mole% phosphatidylserine/95 mole% phosphatidylcholine). The Km for prothrombin obtained at a saturating amount of venom-activated factor Va was nine-fold higher than with thrombin-activated factor V (0.83 microM vs 0.09 microM, respectively) whereas both factor Va molecules stimulated the Vmax of thrombin formation some 6000-fold. Both forms of factor Va promoted the binding factor Xa to negatively charged phospholipid vesicles. However, the apparent Kd for factor Xa was less favorable in the presence of venom-activated factor V (0.67 x 10(-9) M) than in the presence of thrombin-activated factor V (0.043 x 10(-9) M). Thrombin cleaved a peptide bond in the 77,000 mol. wt polypeptide chain of venom-activated factor V, which resulted in the formation of a normal factor Va light chain. This peptide bond cleavage was, however, not associated with a change of cofactor activity. Venom treatment of thrombin-activated factor V, on the other hand, did remove a small fragment (mol. wt approximately 4000) from the heavy chain of factor Va (94,000), yielding a molecule with reduced cofactor activity. The diminished cofactor activity of venom-activated factor V is, therefore, likely due to the fact that a small peptide fragment, involved in the interaction with prothrombin and factor Xa, is missing from the heavy chain of venom-activated factor V.
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PMID:Activation of bovine factor V by an activator purified from the venom of Naja naja oxiana. 144 Jun 44

1. A factor X activator was isolated from the venom of Vipera aspis aspis (Aspic viper) by gel filtration and ion-exchange chromatography. 2. The purified activator has a mol. wt of 75,000 and an isoelectric point of 4.6. Upon reduction, this activator migrated as two bands with mol. wts of 16,000 and 14,000 in sodium dodecyl sulfate polyacrylamide gel electrophoresis. 3. The activator from V. a. aspis venom shortened activated partial thromboplastin time (APTT) of normal plasma and factor IX-deficient plasma from humans. 4. Factor X incubated with isolated activator and calcium ions drastically shortened APTT of factor X-deficient plasma and expressed hydrolytic activity against synthetic substrates for factor Xa, however no hydrolytic activity was detected with the activator alone, indicating that the activator converted factor X to the active form.
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PMID:Isolation and characterization of factor X activator from the venom of Vipera aspis aspis. 228 62

1. Three phospholipase A2s, PLA2-I, PLA2-II and PLA2-III, were isolated from Vipera aspis venom by gel filtration and ion exchange chromatography. 2. Purified PLA2-I, -II and -III have mol. wts of 30,200, 16,000 and 13,500, and isoelectric points of 9.45, 7.65 and less than 4.1, respectively. 3. PLA2-I consists of an acidic subunit (mol. wt 13,700, pI: less than 3.5) and a basic subunit (mol. wt 16,500, pI: 10.6), which can be separated under highly acidic conditions. 4. PLA2-I possessed lethal activity and LD50 for this preparation was estimated to be 0.288 (0.209-0.397) micrograms/g, while lethality was not observed when PLA2-II, -III or each subunit of PLA2-I were administered. 5. Capillary permeability-increasing activity was found in the samples which possessed basic isoelectric points. Additionally, PLA2-I and its basic subunit drastically prolonged activated partial thromboplastin time of platelet rich plasma. 6. Intramuscular injections of PLA2-I, -II and -III increased serum creatine phosphokinase activity in mice, indicating that damage in muscle was caused by these enzymes. 7. NH2-terminal sequences of the three PLA2s were compared with other phospholipase A2s from snake venoms. Furthermore, antigenicities were tested using antiserum prepared against each sample.
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PMID:Comparative study of three phospholipase A2s from the venom of Vipera aspis. 228 65

The procoagulant from Notechis ater niger was purified by gel filtration and anion exchange chromatography. It is a protein with an approximate mol.wt of 58,000 and in the presence of B mercaptoethanol is reduced to two chains with mol.wts of 37,000 and 23,000. The procoagulant has a pI of 7.3. The whole venom requires factor V to be present to bring about coagulation while Ca2+ and phospholipid are not essential, but when present stimulate this process. Normal prothrombin, but not decarboxyprothrombin, is converted by the venom. The activity of the procoagulant from Notechis species has been equated with factor Xa and in this study the similarity is noted, while ecarin-like characteristics in not requiring Ca2+ and phospholipid and an ability to clot heparinised plasma were also noted.
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PMID:Purification and properties of a procoagulant from peninsula tiger snake (Notechis ater niger) venom. 278 77

Venom sac extract of the Oriental hornet significantly prolongs the prothrombin time and the activated partial thromboplastin time both in vitro in human plasma and in vivo in cats. Activity of factors VIII and IX in plasma is reduced to less than 1% within 5 min even with 1 microgram of venom sac extract per ml. The activity of purified factor VIII, as well as semipurified factors IX and X, in factor IX complex was also significantly reduced after incubation with the venom. The decrease of factors II, V, VII, X, XI and XII activity to 9%, 11%, 11%, 29%, 1.7% and 0.7% of normal, respectively, is dose- and time-dependent. Thrombin time, plasma fibrinogen and fibrin degradation products are not affected. The anticoagulant activity is not reversed by dialysis and is abolished completely by heating; it resides mainly in fractions with mol.wts above 5000. The venom has a proteolytic activity on 14C-globin which is partially inhibited by trasylol and ethylenediaminetetraacetic acid. Thus, the venom sac extract exhibits both serine and metaloprotease activities which may affect the activity of the plasma coagulation factors.
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PMID:Effect of venom sac extract of the Oriental hornet (Vespa orientalis) on coagulation factors. 323 1

Two proteins with anticoagulant and antiplatelet activities were purified from Austrelaps superbus (copperhead) venom by gel filtration, ion-exchange and reverse-phase chromatographic methods. These purified proteins were designated superbins I and II. Superbin I was homogeneous, as indicated by electrospray ionization-mass spectrometry, with a mol. wt of 13,252.3 +/- 1.6, whereas superbin II contained two closely related proteins of mol. wts 13,235.5 +/- 1.1 and 13,212.9 +/- 1.2. Both superbins showed phospholipase A2 activity and exhibited weak anticoagulant effects when tested by one-step prothrombin time clotting assays. The 'dissection approach' was used to identify the coagulation complex(es) inhibited by these enzymes in the extrinsic coagulation cascade. The results indicate that both the enzymes inhibit the extrinsic tenase complex, but not the prothrombinase complex, similarly to other weakly anticoagulant phospholipases. Superbins I and II also inhibited aggregation of human platelets induced by collagen.
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PMID:Isolation and purification of superbins I and II from Austrelaps superbus (copperhead) snake venom and their anticoagulant and antiplatelet effects. 927 73