Snake Venom Proteases, Structure-Function Relationship and Effects on Blood Coagulation

Zhang Yun, Xiong Yuliang

Abstract


Snake venoms are probably the most highly concentrated secretion products found in vertebrate. Furthermore, proteases are in a unique position in snake venoms, especially in Crotalid and Viperid venoms. Biologically, proteolytic enzymes may contribute in two ways: the immobilization of the prey and the digestion of prey organism. They are responsible for the hemorrhage, shock, or disorder of blood coagulation after envenomation. They act, by activating, inactivating, or other converting effects, on almost all the components of hemostatic and fibrinolytic systems. Biochemically, they can be mainly classified into two groups: serine proteases, which are inhibited by phenylmethanesulfonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP). Their sequences are homologous to trypsin-kallikrein serine proteases. They share a common active site geometry and enzymatic mechanism but variation of primary sequences out of active center results in the differences of substrate specificities and further the difference of biological and pharmacological activities. Metalloproteinases, which are inhibited by metal chelating reagent (EDTA), are zinc-dependent. Up to now, sequence data indicate that they belong to a new metalloproteinase subfamily which has no significant sequence similarities with any other know metalloproteinases except for a conservative zinc-chelating sequence His-Glu-X-X-His. Because of their common and unique properties compared to their physiological corresponding factors, snake venom proteases have find a position uniquely in hemostasis and thrombosis, both in research and application.


Keywords


snake venom; protease, blood coagulation

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References


Amphlett G. W., Byrne R., and Castellino F. J. (1982), «Cation binding properties of the multiple subforms of RVV-X, the coagulant protein from Vipera russelli», Biochemistry, 21, 125 – 132.

Aragon-Ortiz F. and Gubensek F. (1987), «Characterization of a metalloproteinase from Bothrops asper (Terciopelo) snake venom», Toxicon, 25, 759 – 766.

Assakura M. T., Reichl A. P., Asperti C. A., and Mandelbaum F. R. (1985), «Isolation of the major proteolytic enzyme from the Bothrops moojeni», Toxicon, 21, 691 – 706.

Bjarnason J. B., Barish A., Direnzo G. S., Campbell R., and Fox J. W. (1983), «Kallikrein-like enzyme from Crotalus atrox venom», J. Biol. Chem., 258, 12566 – 12573.

Blasi F., Vassali J. D., and Dano K. (1987), «Urokinase-type plasminogen activator: proenzyme, receptors and inhibitors», J. Cell Biol., 104, 801 – 804.

Bon C. and Zhang Y. (1992), Polypeptide Activit Thrombolytique, Patent of l’Institut Pasteur and Institut National de la Santé et de la Recherche Médicale, No. 92.03467.

Craik C. S., Roczniak S., Largman C., and Rutter W. J. (1987), «The catalytic role of the active site aspartic acid in serine proteases», Science, 237, 909 – 913.

David C., Hill-Eubanks, Carlo G. P., and Lollar P. (1989), «Differential proteolytic activation of factor VIII-vonWillebrand factor complex by thrombin», Proc. Natl. Acad. Sci. USA, 86, 6508 – 6512.

Davie E. W. and Ratnoff O. D. (1964), «Waterfall sequence for intrinsic blood clotting», Science, 145, 1310 – 1312.

Davie E. W., Fujikawa K., and Kisiel W. (1991), «The coagulation cascade: initiation, maintenance, and regulation», Biochemistry, 30, 10364 – 10370.

Dixon G. H., Go S., and Neurath H. (1956), «Peptides combined with 14C-diisopropylphosphoryl following degradation of HC-DIP-trypsin with α-chymotrypsin», Biochim. Biophys. Acta, 19, 193 – 195.

Eaton D., Rodriguez H., and Vehar G. A. (1986), «Proteolytic processing of human factor VIII. Correlation of specific cleavages by thrombin, factor Xa, and activated protein C with activation and inactivation of factor VIII coagulant activity», Biochemistry, 25, 505 – 512.

Esmon C. T. and Jackson C. M. (1973), «The factor V activating enzyme of Russell’s viper venom», Thrombosis Res., 2, 509 – 524.

Esmon C. T. and Owen W. G. (1981), «Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C», Proc. Natl. Acad. Sci. USA, 78, 2249 – 2252.

Farid T. M. and Tu A. T. (1989), «Characterization of cerastobin, a thrombin-like enzyme from the venom of Cerastes vipera», Biochemistry, 28, 371 – 377.

Fischer B. and Will H. (1990), «Effects of intact fibrin and partially plasmin-degraded fibrin on kinetic properties of one-chain tissue-type plasminogen activator», Biochim. Biophys. Acta, 1041, 48 – 54.

Funk C., Gmur J., Herold R., and Straub P. W. (1971), «Reptilase-R, a new reagent in blood coagulation», Br. J. Haematol., 21, 43 – 49.

Furie B. C. and Furie B. (1976), «Coagulation protein of Russell’s viper venom», in: L. Lorand (ed.), Methods in Enzymology, Vol. 45. Acad. Press, New York, pp. 191 – 212.

Furukawa Y., Matsunaga Y., and Hayashi K. (1976), «Purification and characterization of a coagulant protein from the venom of Russell’s viper», Biochim. Biophys. Acta, 1453, 48 – 61.

Guan L. F., Zhang X., and Chi C. W. (1988), «Differences in fibrin polymerization and fibrinopeptide A and B release induced by human thrombin and by the thrombin-like enzyme from the venom of Agkistrodon halys Pallas», in: H. Pirkle and F. S. Markland (eds.), Hemostasis and Animal Venoms, Marcel Dekker Press, New York, pp. 93 – 106.

Gunzler W. A., Steffens G. J., Otting F., Kim S. M., Frankus E., and Flohe L. (1982), «The primary structure of high molecular mass urokinase from human urine: the complete amino acid sequence of the A chain», Hoppe-Seyler’s Zeitschrift Physiol. Chemie, 363, 1155 – 1165.

Higgins D. G. and Sharp P. M. (1989), «Fast and sensitive multiple sequence alignments on a microcomputer», CABIOS, 5, 151 – 153.

Hofmann H. and Bon C. (1987a), «Blood coagulation induced by the venom of Bothrops atrox. I. Identification, purification and properties of a prothrombin activator», Biochemistry, 26, 772 – 780.

Hofmann H. and Bon C. (1987b), «Blood coagulation induced by the venom of Bothrops atrox. II. Identification, purification and properties of two factor X activators», Biochemistry, 26, 780 – 787.

Hoylaerts M., Rijken D. C., Lijnen H. R., and Collen D. (1982), «Kinetics of the activation of plasminogen by human tissue plasminogen activator: role of fibrin», J. Biol. Chem., 257, 2912 – 2919.

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.

Itoh N., Tanaka N., Funakoshi I., Kawasaki T., Mihashi S., and Yamashina I. (1988), «Organization of the gene for batroxobin, a thrombin-like snake venom enzyme», J. Biol. Chem., 263, 7628 – 7631.

Jenny R. J., Pittman D. D., Toole J. J., et al. (1987), «Complete cDNA and derived amino acid sequence of human factor V», Proc. Natl. Acad. Sci. USA, 84, 4846 – 4851.

Kane W. H. and Davie E. W. (1986), «Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin», Proc. Natl. Acad. Sci. USA, 83, 6800 – 6804.

Kane W. H. and Davie E. W. (1988), «Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders», Blood, 71, 539 – 555.

Kirby E. P., Niewiarowski S., Stocker K., Kettner C., and Shaw E. (1979), «Thrombocytin, a serine protease from Bothrops atrox venom. I. Purification and characterization of the enzyme», Biochemistry, 18, 3564 – 3570.

Kisiel W., Hermodson M. A., and Davie E. W. (1976), «Factor X activating enzyme from Russell’s viper venom: isolation and characterization», Biochemistry, 15, 4901 – 4906.

Kisiel W. (1979), «Molecular properties of the factor V-activating enzyme from Russell’s viper venom», J. Biol. Chem., 254, 12230 – 12234.

Kisiel W. and Canfield W. M. (1981), «Snake venom proteases that activate blood coagulation factor V», in: L. Lorand (ed.), Methods in Enzymology, Vol. 80, Acad. Press, New York, pp. 275 – 284.

Kisiel W., Kondo S., Smith K. J., McMullen B. A., and Smith L. F. (1987), «Characterization of a protein C activator from Agkistrodon contortrix contortrix venom», J. Biol. Chem., 262, 12607 – 12613.

Komori Y., Nikai T., and Sugihara H. (1988), «Biochemical and physiological studies on a kallikrein-like enzyme from the venom of Crotalus viridis viridis (Prairie rattlesnake)», Biochim. Biophys. Acta, 967, 92 – 102.

Kraut J. (1977), «Serine proteases: structure and mechanism of catalysis», Ann. Rev. Biochem., 46, 331 – 358.

Kurachi K. and Davie E. W. (1982), «Isolation and characterization of acDNA coding for human factor IX», Proc. Natl. Acad. Sci. USA, 79, 6461 – 6464.

Lee C. Y. and Lee S. (1979), «Cardiovascular effects of snake venoms», in: C. Y. Lee (ed.), Snake Venoms, Springer-Verlag, Berlin, pp. 547 – 590.

Liu N. K. and Xiong Y. L. (1990), «Purification and characterization of thrombin-like enzymes from the venom of Trimeresurus stejnegeri», Zool. Res. (China), 11, 234 – 240 [in Chinese].

Lollar P., Parker C. G., Kajenski P. K., Litwiller R. D., and Pass D. N. (1987), «Degradation of coagulation proteins by an enzyme from Malayan Pit Viper (Agkistrodon rhodostoma) venom», Biochemistry, 26, 7627 – 7636.

Markland F. S., Kettner C., Schiffman S., et al. (1982), «Kallikrein-like activity of crotalase, a snake venom enzyme that clots fibrinogen», Proc. Natl. Acad. Sci. USA, 79, 1688 – 1692.

Magnusson S., Peterson T. W., Sottrup-Jensen L., and Claeys H. (1975), «Complete primary structure of prothrombin: Isolation, structure and reactivity of ten carboxylated glutamic acid residues and regulation of prothrombin activation by thrombin», in: E. Reich, D. B. Rifkin, and E. Shaw (eds.), Proteases and Biological Control, Cold Spring Harbor Laboratory, Cold Spring Harbor Press, New York, pp. 123 – 149.

McMullen B. A., Fujikawa K., and Kisiel W. (1989), «Primary structure of a protein C activator from Agkistrodon contortrix contortrix venom», Biochemistry, 28, 674 – 679.

Meier J. and Nowak G. (1989), «Biochemical and pharmacological investigation of Echis carinatus venoms from three different geographical regions», Toxicon, 28, 159.

Meier J. and Stocker K. (1991), «Effects of snake venoms on hemostasis», CRC Crit. Rev. Toxicol., 21, 171 – 182.

Miyata T., Takeya H., Ozeki Y., et al. (1989), «Primary structure of hemorrhagic protein, HR2a, isolated from the venom of Trimeresurus flavoviridis», J. Biochem. (Jap.), 105, 847 – 853.

Morita T. and Iwanaga S. (1978), «Purification and properties of the prothrombin activator from the venom of Echis carinatus», J. Biochem. (Jap.), 83, 559 – 570.

Neurath H. (1984), «Evolution of proteolytic enzymes», Science, 224, 350 – 357.

Neurath H. (1989), «The diversity of proteolytic enzymes», in: R. J. Beynon and J. S. Bond (eds.), Proteolytic Enzymes. A Practical Approach, IRL Press at Oxford Univ., London, pp. 1 – 12.

Niewiarowski S., Kirby E. D., Brudzynski T. M., and Stocker K. (1979), «Thrombocytin, a serine protease from Bothrops atrox venom. 2. Interaction with platelets and plasma-dotting factors», Biochemistry, 18, 3570 – 3577.

Nikai T., Katano E., Komori Y., and Sugihara H. (1988), «β-fibrinogenase from the venom of Agkistrodon p. piscivorus», Comp. Biochem. Physiol., 89B, 509 – 515.

Orthner C. L., Bhattacharya P., and Strickland D. K. (1988), «Protein C activator from the venom of Agkistrodon contortrix contortrix», Biochemistry, 27, 2558 – 2564.

Ouyang C., Hong J. S., and Teng C. M. (1971), «Purification and properties of the thrombin-like principle of Agkistrodon acutus venom and its comparison with bovine thrombin», Thrombos. Diathes. Haemorrhag., 26, 224 – 234.

Ouyang C., Teng C. M., and Chen Y. C. (1977), «Physicochemical properties of α- and β-fibrinogenases of Trimeresurus mucrosquamatus venom», Biochim. Biophys. Acta, 481, 622 – 630.

Ouyang C., Teng C. M., and Huang T. F. (1987), «Characterization of snake venom principles affecting blood coagulation and platelet aggregation», Asia Pacific J. Pharmacol., 2, 169 – 179.

Patthy L. (1983), «Evolution of the proteases of blood coagulation and fibrinolysis by assembly from modules», Cell, 41, 657 – 663.

Patthy L. (1990), «Evolutionary assembly of blood coagulation proteins», Sem. Thrombos. Hemostas., 16, 245 – 239.

Pennica D., Holmes W. E., Kohr W. J., et al. (1983), «Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli», Nature (Lond.), 301, 214 – 221

Petersen L. C., Lund L. R., Nielsen L. S., Dano K., and Skriver L. (1988), «One-chain urokinase-type plasminogen activator from human sarcoma cells is a proenzyme with little or no intrinsic activity», J. Biol. Chem., 263, 11189 – 11195.

Phillips L. L., Weiss H. J., and Christy N. P. (1973), «Effects of puff adder venom on the coagulation mechanism II, in vitro», Thrombos. Diathes. Haemorrhag., 30, 499 – 508.

Pirkle H. (1988), «Gabonase», in: H. Pirkle and F. S. Markland (eds.), Hemostasis and Animal Venoms, Marcel Dekker Press, New York, pp. 117 – 120.

Pirkle H. and Theodor I. (1988), «Thrombin-like enzymes in the study of fibrin formation», in: H. Pirkle and F. S. Markland (eds.), Hemostasis and Animal Venoms, Marcel Dekker Press, New York, pp. 121 – 141.

Pirkle H. and Theodor I. (1991), «Thrombin-like enzymes from snake venoms», in: A. T. Tu (ed.), Handbook of Natural Toxins. Vol. 5. Reptile Venoms and Toxins, Pergamon Press, New York, pp. 225 – 252.

Rawala R., Saraswathi S., Niewiarowski S., and Colman R. W. (1978), «Molecular changes during the activation of bovine factor V by snake venom proteases», Circulation, 28, 201 – 209.

Robbins K. C., Summaria L., Hsieh B., and Shah R. J. (1967), «The peptide chains of human plasmin», J. Biol. Chem., 242, 2333 – 2342.

Shannon J. D., Baramova E. N., Bjarnason J. B., and Fox J. W. (1989), «Amino acid sequence of a Crotalus atrox venom metalloproteinase which cleaves type IV collagen and gelatin», J. Biol. Chem., 264, 11575 – 11583.

Shaw E., Mares-Guia M., and Cohen W. (1965), «Evidence for an active-center histidine in trypsin through use of a specific reagent, 1-chloro-3-tosylamido-7-afflino-2-heptanone, the chloromethyl ketone derived from Nα-tosyl-L-lysine», Biochemistry, 4, 2219 – 2224.

Shieh T. G., Kawabata S. I., Kihara H., Ohno M., and Iwanaga S. (1988), «Amino acid sequence of a coagulant enzyme, flavoxobin, from Trimeresurus flavoviridis venom», J. Biochem. (Jap.), 103, 596 – 605.

Steffens G. J., Gunzler W. A., Otting F., Frankus E., and Flohe L. (1982), «The complete amino acid sequence of low molecular mass urokinase from human urine», Hoppe-Seyler’s Zeitschrift Physiol. Chemie, 363, 1043 – 1058.

Stocker K., Fischer H., Meier J., Brogli M., and Svendsen L. (1986), «Protein C activators in snake venom», Behring Inst. Mitteilungen, 79, 37 – 47.

Stocker K. and Meier J. (1988), «Thrombin-like snake venom enzymes», in: H. Pirkle and F. S. Markland (eds.), Hemostasis and Animal Venoms, Marcel Dekker Press, New York, pp. 67 – 84.

Stocker K. (1990), «Snake venom proteins affecting hemostasis and fibrinolysis», in: K. Stocker (ed.), Medical Use of Snake Venom Proteins, CRC Press, Florida, pp. 97 – 160.

Sugihara H., Kishida M., and Nikai T. (1986), «Comparative study of four arginine ester hydrolases, ME-1, 2, 3, and 4 from the venom of Trimeresurus mucrosquamatus (The Chinese habu snake)», Comp. Biochem. Physiol., 83B, 743 – 750.

Swift G. H., Dagorn J. C., Ashley P. L., Cummings S. W., and MacDonald R. J. (1982), «Rat pancreatic kallikrein mRNA: Nucleotide sequence of the encoded preproenzyme», Proc. Natl. Acad. Sci. USA, 79, 7263 – 7267.

Takeya H., Arakawa M., Miyata T., Iwanaga S., and Omori-Satoh T. (1989), «Primary structure of Hz-proteinase, a non-hemorrhagic metalloproteinase, isolated from the venom of the habu snake, Trimeresurus flavoviridis», J. Biochem., 106, 131 – 157.

Takeya H., Onikura A., Nikai T., Sugihara H., and Iwanaga S. (1990a), «Primary structure of a hemorrhagic metalloproteinase, HT-2, isolated from the venom of Crotalus ruber ruber», J. Biochem., 108, 711 – 719.

Takeya H., Oda K., Miyata T. Omori-Satoh T., and Iwanaga S. (1990b), «The complete amino acid sequence of the high molecular mass hemorrhagic protein HR1B isolated from the venom of Trimeresurus flavoviridis», J. Biol. Chem., 265, 16068 – 16070.

Tanizaki M. M., Zingali R. B., Kawazaki H., Imajoh S., Yamazaki S., and Suzuki K. (1989), «Purification and some characteristics of a zinc metalloprotease from the venom of Bothrops jararaca ( jararaca)», Toxicon, 27, 747 – 755.

Tans G., Govers-Riemslag J. W. P., Van Rijn J. L. M. L., and Rosing J. (1985), «Purification and properties of a prothrombin activator from the venom of Notechis scutatus scutatus», J. Biol. Chem., 260, 9366 – 9372.

Titani K., Ericsson L. H., Neurath H., and Walsh K. A. (1975), «Amino acid sequence of dogfish trypsin», Biochemistry, 14, 1358 – 1366.

Tokunaga F., Nagasawa K., Tamura S., Miyata T., Iwanaga S., and Kisiel W. (1988), «The factor V-activating enzyme (RVV-V) from Russell’s viper venom. Identification of isoproteins RVV-Va, -Vb and -Vr and their complete amino acid sequence», J. Biol. Chem., 263, 17471 – 17481.

Tu A. T. (1988), «Hemorrhagic proteases from snake venoms», in: H. Pirkle and F. S. Mark land (eds.), Hemostasis and Animal Venoms, Marcel Dekker Press, New York, pp. 425 – 443.

Walker F. J., Owen W. G., and Esmon C. T. (1980), «Characterization of the prothrombin activator from the venom of Oxyuranus scutellatus scutellatus (Taipan venom)», Biochemistry, 19, 1020 – 1023.

Wang W. Y., Xiong Y. L., Yang S. C., and Yang S. L. (1982), «Studies on fibrinolytic constituent separated from Trimeresurus mucrosquamatus venom», Acta Herpetol. Sinica, 3, 45 – 49 [in Chinese].

Weitz J. I., Cruickshank M. K., Thong B., Leslie B., Levine M. N., Ginsberg J., and Eckhardt T. (1988), «Human tissue-type plasminogen activator releases fibrinopeptides A and B from fibrinogen», J. Clin. Invest., 82, 1700 – 1707.

Weitz J. I. and Leslie B. (1990), «Urokinase has direct catalytic activity against fibrinogen and renders it less clottable by thrombin», J. Clin. Invest., 86, 203 – 212.

Wilbur W. J. and Lipman D. J. (1983), «Rapid similarity searches of nucleic acid and protein date banks», Proc. Natl. Acad. Sci. USA, 80, 726 – 730.

Willis T. W. and Tu A. T. (1988), «Purification and biochemical characterization of atroxase, a nonhemorrhagic fibrinolytic protease from western diamondback rattlesnake venom», Biochemistry, 27, 4769 – 4777.

Xiong Y. L. (1979), «Experimental studies on treatment of Viperidae snake bite with trypsin», Acta Pharm. Sinica, 14, 385 – 388 [in Chinese].

Zhang Y. and Xiong Y. L. (1991), «Purification and Characterization of a new fibrinogenase from the venom of the Chinese habu snake (Trimeresurus mucrosguamatus)», Zool. Res. (China), 12, 199 – 207.

Zhang Y., Xiong Y. L., and Bon C. (1992a), «Effects of Chinese snake venoms on blood coagulation, purified coagulation factors and synthetic chromogenic substrates», Asiatic Herpetol. Res.

Zhang Y., Xiong Y. L., and Bon C. (1992b), «Venom plasminogen activator (sv-PA) from the snake venom of Trimeresurus stejnegeri», in: Zhang Yun, Snake Venom Proteases. Structure-Function Relationship and Effects on Blood Coagulation. Ph. D. Thesis, Kunming Institute of Zoology, Academia Sinica, pp. 47 – 89.

Zhang Y., Xiong Y. L., and Bon C. (1992c), «An activating enzyme of blood clotting factor X from the venom of Bungarus fasciatus», in: Zhang Yun, Snake Venom Proteases. Structure-Function Relationship and Effects on Blood Coagulation. Ph. D. Thesis, Kunming Institute of Zoology, Academia Sinica, pp. 90 – 120.




DOI: https://doi.org/10.30906/1026-2296-1998-5-2-113-126

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