Thrombin-like enzymes

Blood/gout/ batraxobin/thrombin-like enzyme Reptilase/ Botrox atrax (L.)... 

Zhao, H.Y., et al. 2002. Effect of electroporation and iontophoresis on skin permeation of Defi-brase—a purified thrombin-like enzyme from the venom of Agkistrodon halys ussuriensis Emelia-nov. Pharmazie 57 482. 

Viperidae endopeptidase, factor X activator, fibrinogenase, kininogenase, metalloproteinase, prothrombin activator, serine protease, thrombin-like enzyme... 

Svendsen, L., Blomback, M., and Olsson, P., Synthetic chromogenic substrates for determination of trypsin and thrombin-like enzymes. Thromb. Bes. I, 267-278 (1972). 

F. Markwardt and G. Nowak. The influence of drugs on disseminated intravascular coagulation (DIC), IV. Effects of the thrombin like enzyme batroxobin on thrombin induced DIC in rats. Thromb. Res. 77 103 (1980). 

Anticoagulant thrombin-like enzyme found in venom of Malayan pit viper, Agkistrodon rhodostoma. 

Bothrops venom proteinase rcpttlase R Botropasc Dcfibrase Reptilase. Thrombin-like enzyme from the venom of Bothrops atrox (Linn.), a pit viper found in several varieties in Southern and Central America. Prepn of cone extract from B. jararaca venom and coagulative properties D. von... 

However, it is evident that the presence of calcium ions is not the only factor to be considered in this sort of phenomenon. Thrombin, like all the other enzymes, is very sensitive to the physical and chemical condition of the medium, and if we expect to obtain check results by mixing serum with distilled water, it is much to be feared that we shall obtain irregular and even contradictory results if instead of distilled water we take another serum, especially an old serum, since the chemical composition... 

A. Thrombin-Like Enzymes. Because the high coagulant activity of Malayan pit viper venom, the thrombin-like enzyme arvin (ancrod) was isolated from this venom. Arvin has been extensively studied because it is used as a therapeutic drug for diseases such as thrombosis or myocardial infarction, which involve fibrinogen. 

Although arvin is frequently called a thrombin-like enzyme, it is not identical to thrombin. The notable difference is that arvin does not give peptide B as a product when fibrin is formed. Fibrinogen consists of a subunit that contains three polypeptide chains, Aa, Bp, and y. When thrombin hydrolyzes the A-terminal arginyl-glycine bonds of the Aa and Bp chains, fibrinopeptides A and B are released. The remaining portion of fibrinogen polymerizes to form fibrin, which is a blood clot. 

Thrombin-like enzymes are relatively common, are isolated from many other pit viper and viper venoms, and are called by different names such as reptilase, batroxobin, crotalase, or are simply called thrombin-like enzyme. Unlike thrombin, these thrombinlike enzymes affect factor XIII in a variable way ancrod activates the factor very slowly, whereas reptilase does so more quickly. 

A snake venom is a rich source of enzymes. Many enzymes are purified from snake venoms and sold commercially. These include phosphodiesterase, L-amino acid oxidase, 5 -nucleotidase, thrombin-like enzymes (ancrod, atroxin, crotalase, reptilase), and thrombo-cytin. 

D. Thrombin-Like Enzymes. Ancrod (arvin), a very specific snake venom component, has been investigated extensively for its anticoagulant action. Ancrod is a very specific protease whose action has some similarity to that of thrombin and occurs in the terminal sequence of a complex blood coagulation mechanism. Ancrod hydrolyzes only the Aa chain of fibrinogen and produces a polymer of the type (a Bp y)n rather than the (aPy)n type normal fibrin clot. The microclot produced by ancrod from fibrinogen is readily hydrolyzed by plasmin that was activated from tissue plasminogen. This results in a defibrination effect. This property is extensively used in the treatment of a patient who has suffered from myocardial infarction. 

Itoh, N., Tanaka, N., Mihashi, S., and Yamashina, I. (1987). Molecular cloning and sequence analysis of cDNA for batroxobin, a thrombin-like snake venom enzyme. J. Biol. Chem. 262 3132-3135. 

Gaffney, P.J., 1977, International committee communications. Report of the task force on standards for thrombin and thrombin like enzymes. Thromb Haemostas, 38 562. 

Some boronic acid-based enzyme inhibitors undergo strong yet reversible covalent attachment to a nucleophile at the enzyme s active site, while others simply act as competitive inhibitors in their borate conjugate base form. Boronic acid-based inhibition of thrombin has been achieved <93MI109>, and that of P-lactamases has been particularly effective <95TL8399, 96M1688>. When compared to other covalent transition-state analog inhibitors of P-lactamases like phos-... 

From study of peptides formed by partial hydrolysis of the 32P-labeled chymotrypsin, the sequence of amino acids surrounding the reactive serine was established and serine 195 was identified as the residue whose side chain hydroxyl group became phosphorylated. The same sequence Gly-Asp-Ser-Gly was soon discovered around reactive serine residues in trypsin, thrombin, elastase, and in the trypsin-like cocoonase used by silkmoths to escape from their cocoons.198 We know now that these are only a few of the enzymes in a very large family of serine proteases, most of which have related active site sequences.199 200 Among these are thrombin and other enzymes of the blood-clotting cascade (Fig. 12-17), proteases of lysosomes, and secreted proteases. 

Thrombin activable fibrinolysis inhibitor (TAFI) is a plasma protein that is activated by thrombin in the presence of thrombomodulin to a labile carboxypeptidase-B-like enzyme that inhibits fibrinolysis. When TAFIa is included in a clot undergoing lysis induced by tPA and plasminogen, the time to achieve lysis is prolonged and free lysine and arginine are released (Wang et al., 1998). TAFIa retards the fibrin-enhanced activation of plasminogen by tPA and inhibits the accumulation of plasminogen at the lysis front (Sakharov et al., 1997). 

Like antithrombin, heparin cofactor II inhibits proteases by forming a I I stoichiometric complex with the enzyme. The protease attacks the reactive site of heparin cofactor II located on the C-terminus, resulting in the formation of a covalent bond. Heparin cofactor II has higher protease specificity than antithrombin. Of the coagulation enzymes, heparin cofactor II is known only to inhibit thrombin (92). Additionally heparin cofactor II has been shown to inhibit chymotrypsin (93) and leukocyte cathepsin G (94), This protease specificity appears to be due to the active site bond present in heparin cofactor II. Whereas antithrombin contains an Arg-Ser bond as its active site, heparin cofactor II is unique in containing a Leu-Ser bond. This suggests than another portion of the heparin cofactor II molecular may be required for protease binding,... 

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