Advertisement

Cellular and Molecular Life Sciences

, Volume 66, Issue 17, pp 2851–2871 | Cite as

Protein complexes in snake venom

  • R. Doley
  • R. M. Kini
Review

Abstract

Snake venom contains mixture of bioactive proteins and polypeptides. Most of these proteins and polypeptides exist as monomers, but some of them form complexes in the venom. These complexes exhibit much higher levels of pharmacological activity compared to individual components and play an important role in pathophysiological effects during envenomation. They are formed through covalent and/or non-covalent interactions. The subunits of the complexes are either identical (homodimers) or dissimilar (heterodimers; in some cases subunits belong to different families of proteins). The formation of complexes, at times, eliminates the non-specific binding and enhances the binding to the target molecule. On several occasions, it also leads to recognition of new targets as protein-protein interaction in complexes exposes the critical amino acid residues buried in the monomers. Here, we describe the structure and function of various protein complexes of snake venoms and their role in snake venom toxicity.

Keywords

PLA2 complexes Metalloprotease complexes Dimeric disintegrin Serine protease complexes Covalent and non-covalent three-finger toxin Synergistic three-finger toxin 

Notes

Acknowledgments

This work was supported by grants from the Biomedical Research Council (BMRC) of Singapore. We thank Cho Yeow Koh for preparing Fig. 6. The authors thank the anonymous reviewers for their constructive comments.

References

  1. 1.
    Slotta K, Fraenkel-Conrat H (1938) Schlangengifte-III. Mitteilung: Reinigung und Krystallisation des Klapperschlangen-Giftes. Ber Dtsch Chem Ges 71:1076–1081CrossRefGoogle Scholar
  2. 2.
    Kini RM (2003) Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon 42:827–840PubMedCrossRefGoogle Scholar
  3. 3.
    Bon C (1997) Multicomponent neurotoxic phospholipases A2. In: Kini RM (ed) Phospholipase A2 enzyme: structure, function and mechanism. Wiley, Chichester, pp 269–285Google Scholar
  4. 4.
    Chang CC, Lee CY (1963) Isolation of neurotoxins from the venom of Bungarus multicinctus and their modes of neuromuscular blocking action. Arch Int Pharmacodyn Ther 144:241–257PubMedGoogle Scholar
  5. 5.
    Chu CC, Li SH, Chen YH (1995) Resolution of isotoxins in the beta-bungarotoxin family. J Chromatogr A 694:492–497PubMedCrossRefGoogle Scholar
  6. 6.
    Kondo K, Toda H, Narita K, Lee CY (1982) Amino acid sequences of three beta-bungarotoxins (beta 3-, beta 4-, and beta 5- bungarotoxins) from Bungarus multicinctus venom: amino acid substitutions in the A chains. J Biochem 91:1531–1548PubMedGoogle Scholar
  7. 7.
    Chu CC, Chu ST, Chen SW, Chen YH (1994) The non-phospholipase A2 subunit of beta-bungarotoxin plays an important role in the phospholipase A2-independent neurotoxic effect: characterization of three isotoxins with a common phospholipase A2 subunit. Biochem J 303(Pt 1):171–176PubMedGoogle Scholar
  8. 8.
    Kondo K, Toda H, Narita K (1978) Characterization of phospholipase A activity of beta1-bungarotoxin from Bungarus multicinctus venom. I: its enzymatic properties and modification with p-bromophenacyl bromide. J Biochem (Tokyo) 84:1291–1300Google Scholar
  9. 9.
    Bon C, Changeux JP, Jeng TW, Fraenkel-Conrat H (1979) Postsynaptic effects of crotoxin and of its isolated subunits. Eur J Biochem 99:471–481PubMedCrossRefGoogle Scholar
  10. 10.
    Kwong PD, McDonald NQ, Sigler PB, Hendrickson WA (1995) Structure of beta 2-bungarotoxin: potassium channel binding by Kunitz modules and targeted phospholipase action. Structure 3:1109–1119PubMedCrossRefGoogle Scholar
  11. 11.
    Su MJ, Chang CC (1984) Presynaptic effects of snake venom toxins which have phospholipase A2 activity (beta-bungarotoxin, taipoxin, crotoxin). Toxicon 22:631–640PubMedCrossRefGoogle Scholar
  12. 12.
    Harvey AL, Karlsson E (1982) Protease inhibitor homologues from mamba venoms: facilitation of acetylcholine release and interactions with prejunctional blocking toxins. Br J Pharmacol 77:153–161PubMedGoogle Scholar
  13. 13.
    Benishin CG (1990) Potassium channel blockade by the B subunit of beta-bungarotoxin. Mol Pharmacol 38:164–169PubMedGoogle Scholar
  14. 14.
    Wu PF, Wu SN, Chang CC, Chang LS (1998) Cloning and functional expression of B chains of beta-bungarotoxins from Bungarus multicinctus (Taiwan banded krait). Biochem J 334(Pt 1):87–92PubMedGoogle Scholar
  15. 15.
    Chu ST, Chu CC, Tseng CC, Chen YH (1993) Met-8 of the beta 1-bungarotoxin phospholipase A2 subunit is essential for the phospholipase A2-independent neurotoxic effect. Biochem J 295(Pt 3):713–718PubMedGoogle Scholar
  16. 16.
    Chang LS, Yang CC (1988) Role of the N-terminal region of the A chain in beta 1-bungarotoxin from the venom of Bungarus multicinctus (Taiwan-banded krait). J Protein Chem 7:713–727PubMedCrossRefGoogle Scholar
  17. 17.
    Petersen M, Penner R, Pierau FK, Dreyer F (1986) Beta-bungarotoxin inhibits a non-inactivating potassium current in guinea pig dorsal root ganglion neurones. Neurosci Lett 68:141–145PubMedCrossRefGoogle Scholar
  18. 18.
    Rehm H, Betz H (1982) Binding of beta-bungarotoxin to synaptic membrane fractions of chick brain. J Biol Chem 257:10015–10022PubMedGoogle Scholar
  19. 19.
    Rehm H, Betz H (1984) Solubilization and characterization of the beta-bungarotoxin-binding protein of chick brain membranes. J Biol Chem 259:6865–6869PubMedGoogle Scholar
  20. 20.
    Tsai IH, Lu PJ, Wang YM, Ho CL, Liaw LL (1995) Molecular cloning and characterization of a neurotoxic phospholipase A2 from the venom of Taiwan habu (Trimeresurus mucrosquamatus). Biochem J 311(Pt 3):895–900PubMedGoogle Scholar
  21. 21.
    Santos KF, Murakami MT, Cintra AC, Toyama MH, Marangoni S, Forrer VP, Brandao N Jr, Polikarpov I, Arni RK (2007) Crystallization and preliminary X-ray crystallographic analysis of the heterodimeric crotoxin complex and the isolated subunits crotapotin and phospholipase A2. Acta Crystallogr Sect F Struct Biol Cryst Commun 63:287–290PubMedCrossRefGoogle Scholar
  22. 22.
    Faure G, Guillaume JL, Camoin L, Saliou B, Bon C (1991) Multiplicity of acidic subunit isoforms of crotoxin, the phospholipase A2 neurotoxin from Crotalus durissus terrificus venom, results from posttranslational modifications. Biochemistry 30:8074–8083PubMedCrossRefGoogle Scholar
  23. 23.
    Wu SH, Chang FH, Tzeng MC (1983) Separation of the subunits of crotoxin by high-performance liquid chromatography. J Chromatogr 259:375–377PubMedCrossRefGoogle Scholar
  24. 24.
    Aird SD, Kaiser II, Lewis RV, Kruggel WG (1985) Rattlesnake presynaptic neurotoxins: primary structure and evolutionary origin of the acidic subunit. Biochemistry 24:7054–7058PubMedCrossRefGoogle Scholar
  25. 25.
    Faure G, Choumet V, Bouchier C, Camoin L, Guillaume JL, Monegier B, Vuilhorgne M, Bon C (1994) The origin of the diversity of crotoxin isoforms in the venom of Crotalus durissus terrificus. Eur J Biochem 223:161–164PubMedCrossRefGoogle Scholar
  26. 26.
    Marchi-Salvador DP, Correa LC, Magro AJ, Oliveira CZ, Soares AM, Fontes MR (2008) Insights into the role of oligomeric state on the biological activities of crotoxin: crystal structure of a tetrameric phospholipase A2 formed by two isoforms of crotoxin B from Crotalus durissus terrificus venom. Proteins 72:883–891PubMedCrossRefGoogle Scholar
  27. 27.
    Habermann E, Breithaupt H (1978) Mini-review: the crotoxin complex—an example of biochemical and pharmacological protein complementation. Toxicon 16(1):9–30CrossRefGoogle Scholar
  28. 28.
    Hendon RA, Tu AT (1979) The role of crotoxin subunits in tropical rattlesnake neurotoxic action. Biochim Biophys Acta 578:243–252PubMedGoogle Scholar
  29. 29.
    Gopalakrishnakone P, Hawgood BJ (1984) Morphological changes induced by crotoxin in murine nerve and neuromuscular junction. Toxicon 22:791–804PubMedCrossRefGoogle Scholar
  30. 30.
    Gutierrez JM, Ponce-Soto LA, Marangoni S, Lomonte B (2008) Systemic and local myotoxicity induced by snake venom group II phospholipases A2: comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue. Toxicon 51:80–92PubMedCrossRefGoogle Scholar
  31. 31.
    Sampaio SC, Brigatte P, Sousa-e-Silva MC, dos-Santos EC, Rangel-Santos AC, Curi R, Cury Y (2003) Contribution of crotoxin for the inhibitory effect of Crotalus durissus terrificus snake venom on macrophage function. Toxicon 41:899–907PubMedCrossRefGoogle Scholar
  32. 32.
    Sampaio SC, Rangel-Santos AC, Peres CM, Curi R, Cury Y (2005) Inhibitory effect of phospholipase A(2) isolated from Crotalus durissus terrificus venom on macrophage function. Toxicon 45:671–676PubMedCrossRefGoogle Scholar
  33. 33.
    Strong PN, Goerke J, Oberg SG, Kelly RB (1976) Beta-Bungarotoxin, a pre-synaptic toxin with enzymatic activity. Proc Natl Acad Sci USA 73:178–182PubMedCrossRefGoogle Scholar
  34. 34.
    Landucci EC, Condino-Neto A, Perez AC, Hyslop S, Corrado AP, Novello JC, Marangoni S, Oliveira B, Antunes E, de Nucci G (1994) Crotoxin induces aggregation of human washed platelets. Toxicon 32:217–226PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang HL, Han R, Chen ZX, Chen BW, Gu ZL, Reid PF, Raymond LN, Qin ZH (2006) Opiate and acetylcholine-independent analgesic actions of crotoxin isolated from crotalus durissus terrificus venom. Toxicon 48:175–182PubMedCrossRefGoogle Scholar
  36. 36.
    Costa LA, Miles H, Araujo CE, Gonzalez S, Villarrubia VG (1998) Tumor regression of advanced carcinomas following intra- and/or peri-tumoral inoculation with VRCTC-310 in humans: preliminary report of two cases. Immunopharmacol Immunotoxicol 20:15–25PubMedCrossRefGoogle Scholar
  37. 37.
    Donato NJ, Martin CA, Perez M, Newman RA, Vidal JC, Etcheverry M (1996) Regulation of epidermal growth factor receptor activity by crotoxin, a snake venom phospholipase A2 toxin: a novel growth inhibitory mechanism. Biochem Pharmacol 51:1535–1543PubMedCrossRefGoogle Scholar
  38. 38.
    Rudd CJ, Viskatis LJ, Vidal JC, Etcheverry MA (1994) In vitro comparison of cytotoxic effects of crotoxin against three human tumors and a normal human epidermal keratinocyte cell line. Invest New Drugs 12:183–184PubMedCrossRefGoogle Scholar
  39. 39.
    Yan CH, Yang YP, Qin ZH, Gu ZL, Reid P, Liang ZQ (2007) Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells. Acta Pharmacol Sin 28:540–548PubMedCrossRefGoogle Scholar
  40. 40.
    Mebs D, Ownby CL (1990) Myotoxic components of snake venoms: their biochemical and biological activities. Pharmacol Ther 48:223–236PubMedCrossRefGoogle Scholar
  41. 41.
    Kaiser II, Aird SD (1987) A crotoxin homolog from the venom of the Uracoan rattlesnake (Crotalus vegrandis). oxicon 25:1113–1120PubMedCrossRefGoogle Scholar
  42. 42.
    Bieber AL, Tu T, Tu AT (1975) Studies of an acidic cardiotoxin isolated from the venom of Mojave rattlesnake (Crotalus scutulatus). Biochim Biophys Acta 400:178–188PubMedGoogle Scholar
  43. 43.
    Ho CL, Lee CY (1981) Presynaptic actions of Mojave toxin isolated from Mojave rattlesnake (Crotalus scutulatus) venom. Toxicon 19:889–892PubMedCrossRefGoogle Scholar
  44. 44.
    Pool WR, Bieber AL (1981) Fractionation of midget faded rattlesnake (Crotalus viridis concolor) venom: lethal fractions and enzymatic activities. Toxicon 19:517–527PubMedCrossRefGoogle Scholar
  45. 45.
    Straight RC, Glenn JL (1988) Isolation and characterization of basic phospholipase (PLA2) and acidic subunits of canebrake toxin from Crotalus horridus atricaudatus venom using HPLC. Toxicon 27:80Google Scholar
  46. 46.
    Chen YH, Wang YM, Hseu MJ, Tsai IH (2004) Molecular evolution and structure-function relationships of crotoxin-like and asparagine-6-containing phospholipases A2 in pit viper venoms. Biochem J 381:25–34PubMedCrossRefGoogle Scholar
  47. 47.
    Aird SD, Kruggel WG, Kaiser II (1990) Amino acid sequence of the basic subunit of Mojave toxin from the venom of the Mojave rattlesnake (Crotalus s. scutulatus). Toxicon 28:669–673PubMedCrossRefGoogle Scholar
  48. 48.
    Bieber AL, Becker RR, McParland R, Hunt DF, Shabanowitz J, Yates JRIII, Martino PA, Johnson GR (1990) The complete sequence of the acidic subunit from Mojave toxin determined by Edman degradation and mass spectrometry. Biochim Biophys Acta 1037:413–421PubMedGoogle Scholar
  49. 49.
    French WJ, Hayes WK, Bush SP, Cardwell MD, Bader JO, Rael ED (2004) Mojave toxin in venom of Crotalus helleri (Southern Pacific Rattlesnake): molecular and geographic characterization. Toxicon 44:781–791PubMedCrossRefGoogle Scholar
  50. 50.
    Wooldridge BJ, Pineda G, Banuelas-Ornelas JJ, Dagda RK, Gasanov SE, Rael ED, Lieb CS (2001) Mojave rattlesnakes (Crotalus scutulatus scutulatus) lacking the acidic subunit DNA sequence lack Mojave toxin in their venom. Comp Biochem Physiol B Biochem Mol Biol 130:169–179PubMedCrossRefGoogle Scholar
  51. 51.
    Valdes JJ, Thompson RG, Wolff VL, Menking DE, Rael ED, Chambers JP (1989) Inhibition of calcium channel dihydropyridine receptor binding by purified Mojave toxin. Neurotoxicol Teratol 11:129–133PubMedCrossRefGoogle Scholar
  52. 52.
    Chambers JP, Wayner MJ, Dungan J, Rael ED, Valdes JJ (1986) The effects of purified Mojave toxin on rat synaptic membrane (Ca2+ + Mg2+)-ATPase and the dihydropyridine receptor. Brain Res Bull 16:639–643PubMedCrossRefGoogle Scholar
  53. 53.
    Cate RL, Bieber AL (1978) Purification and characterization of Mojave (Crotalus scutulatus scutulatus) toxin and its subunits. Arch Biochem Biophys 189:397–408PubMedCrossRefGoogle Scholar
  54. 54.
    Tchorbanov B, Grishin E, Aleksiev B, Ovchinnikov Y (1978) A neurotoxic complex from the venom of the Bulgarian viper (Vipera ammodytes ammodytes) and partial amino acid sequence of the toxic phospholipase A2. Toxicon 16:37–44PubMedCrossRefGoogle Scholar
  55. 55.
    Mancheva I, Kleinschmidt T, Aleksiev B, Braunitzer G (1987) Sequence homology between phospholipase and its inhibitor in snake venom: the primary structure of phospholipase A2 of vipoxin from the venom of the Bulgarian viper (Vipera ammodytes ammodytes, Serpentes). Biol Chem Hoppe Seyler 368(34):3–352Google Scholar
  56. 56.
    Banumathi S, Rajashankar KR, Notzel C, Aleksiev B, Singh TP, Genov N, Betzel C (2001) Structure of the neurotoxic complex vipoxin at 1.4 A resolution. Acta Crystallogr D Biol Crystallogr 57:1552–1559PubMedCrossRefGoogle Scholar
  57. 57.
    Perbandt M, Wilson JC, Eschenburg S, Mancheva I, Aleksiev B, Genov N, Willingmann P, Weber W, Singh TP, Betzel C (1997) Crystal structure of vipoxin at 2.0 A: an example of regulation of a toxic function generated by molecular evolution. FEBS Lett 412(57):3–577Google Scholar
  58. 58.
    Tchorbanov B, Aleksiev B, Bukolova-Orlova T, Burstein E, Atanasov B (1977) Subfractionation and recombination of a neurotoxic complex from the venom of the Bulgarian viper (Vipera ammodytes ammodytes). FEBS Lett 76:266–268PubMedCrossRefGoogle Scholar
  59. 59.
    Wang YM, Lu PJ, Ho CL, Tsai IH (1992) Characterization and molecular cloning of neurotoxic phospholipases A2 from Taiwan viper (Vipera russelli formosensis). Eur J Biochem 209:635–641PubMedCrossRefGoogle Scholar
  60. 60.
    Freedman JE, Snyder SH (1981) Vipoxin: a protein from Russell’s viper venom with high affinity for biogenic amine receptors. J Biol Chem 256:13172–13179PubMedGoogle Scholar
  61. 61.
    Ovadia M, Kochva E, Moav B (1977) Purification and partial characterization of lethal synergistic components from the venom of Vipera palaestinae. Toxicon 15:549–560PubMedCrossRefGoogle Scholar
  62. 62.
    Simon T, Bdolah A, Kochva E (1980) The two-component toxin of Vipera palaestinae: contribution of phospholipase A to its activity. Toxicon 18:249–259PubMedCrossRefGoogle Scholar
  63. 63.
    Krizaj I, Bdolah A, Gubensek F, Bencina P, Pungercar J (1996) Protein and cDNA structures of an acidic phospholipase A2, the enzymatic part of an unusual, two-component toxin from Vipera palaestinae. Biochem Biophys Res Commun 227:374–379PubMedCrossRefGoogle Scholar
  64. 64.
    Batzri-Izraeli R, Bdolah A (1982) Isolation and characterization of the main toxic fraction from the venom of the false horned viper (Pseudocerastes fieldi). Toxicon 20:867–875PubMedCrossRefGoogle Scholar
  65. 65.
    Tsai MC, Lee CY, Bdolah A (1983) Mode of neuromuscular blocking action of a toxic phospholipase A2 from Pseudocerastes fieldi (Field’s horned viper) snake venom. Toxicon 21:527–534PubMedCrossRefGoogle Scholar
  66. 66.
    Francis B, Bdolah A, Kaiser II (1995) Amino acid sequences of a heterodimeric neurotoxin from the venom of the false horned viper (Pseudocerastes fieldi). Toxicon 33:863–874PubMedCrossRefGoogle Scholar
  67. 67.
    Fohlman J, Eaker D, Karlsoon E, Thesleff S (1976) Taipoxin, an extremely potent presynaptic neurotoxin from the venom of the Australian snake taipan (Oxyuranus s. scutellatus): isolation, characterization, quaternary structure and pharmacological properties. Eur J Biochem 68:457–469PubMedCrossRefGoogle Scholar
  68. 68.
    Lind P, Eaker D (1982) Amino-acid sequence of the alpha-subunit of taipoxin, an extremely potent presynaptic neurotoxin from the Australian snake taipan (Oxyuranus s. scutellatus). Eur J Biochem 124:441–447PubMedCrossRefGoogle Scholar
  69. 69.
    Fohlman J, Lind P, Eaker D (1977) Taipoxin, an extremely potent presynaptic snake venom neurotoxin: elucidation of the primary structure of the acidic carbohydrate-containing taipoxin-subunit, a prophospholipase homolog. FEBS Lett 84:367–371PubMedCrossRefGoogle Scholar
  70. 70.
    Fohlman J (1979) Comparison of two highly toxic Australian snake venoms: the taipan (Oxyuranus s. scutellatus) and the fierce snake (Parademansia microlepidotus). Toxicon 17:170–172PubMedCrossRefGoogle Scholar
  71. 71.
    Hodgson WC, Dal Belo CA, Rowan EG (2007) The neuromuscular activity of paradoxin: a presynaptic neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus). Neuropharmacology 52:1229–1236PubMedCrossRefGoogle Scholar
  72. 72.
    Kuruppu S, Reeve S, Banerjee Y, Kini RM, Smith AI, Hodgson WC (2005) Isolation and pharmacological characterization of cannitoxin, a presynaptic neurotoxin from the venom of the Papuan Taipan (Oxyuranus scutellatus canni). J Pharmacol Exp Ther 315:1196–1202PubMedCrossRefGoogle Scholar
  73. 73.
    Su MJ, Coulter AR, Sutherland SK, Chang CC (1983) The presynaptic neuromuscular blocking effect and phospholipase A2 activity of textilotoxin, a potent toxin isolated from the venom of the Australian brown snake, Pseudonaja textilis. Toxicon 21:143–151PubMedCrossRefGoogle Scholar
  74. 74.
    Pearson JA, Tyler MI, Retson KV, Howden ME (1993) Studies on the subunit structure of textilotoxin, a potent presynaptic neurotoxin from the venom of the Australian common brown snake (Pseudonaja textilis). 3: the complete amino-acid sequences of all the subunits. Biochim Biophys Acta 1161(22):3–229Google Scholar
  75. 75.
    Pearson JA, Tyler MI, Retson KV, Howden ME (1991) Studies on the subunit structure of textilotoxin, a potent presynaptic neurotoxin from the venom of the Australian common brown snake (Pseudonaja textilis). 2: the amino acid sequence and toxicity studies of subunit D. Biochim Biophys Acta 1077(14):7–150Google Scholar
  76. 76.
    Scott DL, White SP, Otwinowski Z, Yuan W, Gelb MH, Sigler PB (1990) Interfacial catalysis: the mechanism of phospholipase A2. Science 250:1541–1546PubMedCrossRefGoogle Scholar
  77. 77.
    Brown AM, Yatani A, Lacerda AE, Gurrola GB, Possani LD (1987) Neurotoxins that act selectively on voltage-dependent cardiac calcium channels. Circ Res 61:I6–I9PubMedGoogle Scholar
  78. 78.
    Possani LD, Martin BM, Yatani A, Mochca-Morales J, Zamudio FZ, Gurrola GB, Brown AM (1992) Isolation and physiological characterization of taicatoxin, a complex toxin with specific effects on calcium channels. Toxicon 30:1343–1364PubMedCrossRefGoogle Scholar
  79. 79.
    Rucavado A, Lomonte B, Ovadia M, Gutierrez JM (1995) Local tissue damage induced by BaP1, a metalloproteinase isolated from Bothrops asper (Terciopelo) snake venom. Exp Mol Pathol 63:186–199PubMedCrossRefGoogle Scholar
  80. 80.
    Gutierrez JM, Romero M, Nunez J, Chaves F, Borkow G, Ovadia M (1995) Skeletal muscle necrosis and regeneration after injection of BaH1, a hemorrhagic metalloproteinase isolated from the venom of the snake Bothrops asper (Terciopelo). Exp Mol Pathol 62:28–41PubMedCrossRefGoogle Scholar
  81. 81.
    Gutierrez JM, Rucavado A (2000) Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage. Biochimie 82:841–850PubMedCrossRefGoogle Scholar
  82. 82.
    Bjarnason JB, Fox JW (1994) Hemorrhagic metalloproteinases from snake venoms. Pharmacol Ther 62:325–372PubMedCrossRefGoogle Scholar
  83. 83.
    Bjarnason JB, Fox JW (1995) Snake venom metalloendopeptidases: reprolysins. Methods Enzymol 248:345–368PubMedCrossRefGoogle Scholar
  84. 84.
    Castro HC, Zingali RB, Albuquerque MG, Pujol-Luz M, Rodrigues CR (2004) Snake venom thrombin-like enzymes: from reptilase to now. Cell Mol Life Sci 61:843–856PubMedCrossRefGoogle Scholar
  85. 85.
    Markland FS (1998) Snake venoms and the hemostatic system. Toxicon 36:1749–1800PubMedCrossRefGoogle Scholar
  86. 86.
    Serrano SM, Maroun RC (2005) Snake venom serine proteinases: sequence homology vs. substrate specificity, a paradox to be solved. Toxicon 45:1115–1132PubMedCrossRefGoogle Scholar
  87. 87.
    Hite LA, Jia LG, Bjarnason JB, Fox JW (1994) cDNA sequences for four snake venom metalloproteinases: structure, classification, and their relationship to mammalian reproductive proteins. Arch Biochem Biophys 308:182–191PubMedCrossRefGoogle Scholar
  88. 88.
    Fox JW, Serrano SM (2008) Insights into and speculations about snake venom metalloproteinase (SVMP) synthesis, folding and disulfide bond formation and their contribution to venom complexity. FEBS J 275:3016–3030PubMedCrossRefGoogle Scholar
  89. 89.
    Fox JW, Serrano SM (2009) Timeline of key events in snake venom metalloproteinase research. J Proteomics 72:200–209PubMedCrossRefGoogle Scholar
  90. 90.
    Kisiel W, Hermodson MA, Davie EW (1976) Factor X activating enzyme from Russell’s viper venom: isolation and characterization. Biochemistry 15:4901–4906PubMedCrossRefGoogle Scholar
  91. 91.
    Morita T (2005) Structures and functions of snake venom CLPs (C-type lectin-like proteins) with anticoagulant-, procoagulant-, and platelet-modulating activities. Toxicon 45:1099–1114PubMedCrossRefGoogle Scholar
  92. 92.
    Takeya H, Nishida S, Miyata T, Kawada S, Saisaka Y, Morita T, Iwanaga S (1992) Coagulation factor X activating enzyme from Russell’s viper venom (RVV-X): a novel metalloproteinase with disintegrin (platelet aggregation inhibitor)-like and C-type lectin-like domains. J Biol Chem 267:14109–14117PubMedGoogle Scholar
  93. 93.
    Gowda DC, Jackson CM, Hensley P, Davidson EA (1994) Factor X-activating glycoprotein of Russell’s viper venom: polypeptide composition and characterization of the carbohydrate moieties. J Biol Chem 269:10644–10650PubMedGoogle Scholar
  94. 94.
    Fujikawa K, Legaz ME, Davie EW (1972) Bovine factor X 1 (Stuart factor): mechanism of activation by protein from Russell’s viper venom. Biochemistry 11:4892–4899PubMedCrossRefGoogle Scholar
  95. 95.
    Takeda S, Igarashi T, Mori H (2007) Crystal structure of RVV-X: an example of evolutionary gain of specificity by ADAM proteinases. FEBS Lett 581:5859–5864PubMedCrossRefGoogle Scholar
  96. 96.
    Yamada D, Sekiya F, Morita T (1996) Isolation and characterization of carinactivase, a novel prothrombin activator in Echis carinatus venom with a unique catalytic mechanism. J Biol Chem 271:5200–5207PubMedCrossRefGoogle Scholar
  97. 97.
    Yamada D, Morita T (1999) CA-1 method, a novel assay for quantification of normal prothrombin using a Ca2+-dependent prothrombin activator, carinactivase-1. Thromb Res 94:221–226PubMedCrossRefGoogle Scholar
  98. 98.
    Yamada D, Morita T (1997) Purification and characterization of a Ca2+-dependent prothrombin activator, multactivase, from the venom of Echis multisquamatus. J Biochem 122:991–997PubMedGoogle Scholar
  99. 99.
    Okuda D, Koike H, Morita T (2002) A new gene structure of the disintegrin family: a subunit of dimeric disintegrin has a short coding region. Biochemistry 41:14248–14254PubMedCrossRefGoogle Scholar
  100. 100.
    Calvete JJ, Moreno-Murciano MP, Theakston RD, Kisiel DG, Marcinkiewicz C (2003) Snake venom disintegrins: novel dimeric disintegrins and structural diversification by disulphide bond engineering. Biochem J 372:725–734PubMedCrossRefGoogle Scholar
  101. 101.
    Bilgrami S, Tomar S, Yadav S, Kaur P, Kumar J, Jabeen T, Sharma S, Singh TP (2004) Crystal structure of schistatin, a disintegrin homodimer from saw-scaled viper (Echis carinatus) at 2.5 A resolution. J Mol Biol 341:829–837PubMedCrossRefGoogle Scholar
  102. 102.
    Moiseeva N, Bau R, Swenson SD, Markland FS Jr, Choe JY, Liu ZJ, Allaire M (2008) Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 1.7 A resolution. Acta Crystallogr D Biol Crystallogr 64:466–470PubMedCrossRefGoogle Scholar
  103. 103.
    Ruoslahti E, Pierschbacher MD (1986) Arg-Gly-Asp: a versatile cell recognition signal. Cell 44:517–518PubMedCrossRefGoogle Scholar
  104. 104.
    Calvete JJ, Marcinkiewicz C, Monleon D, Esteve V, Celda B, Juarez P, Sanz L (2005) Snake venom disintegrins: evolution of structure and function. Toxicon 45:1063–1074PubMedCrossRefGoogle Scholar
  105. 105.
    Calvete JJ (2005) Structure-function correlations of snake venom disintegrins. Curr Pharm Des 11:829–835PubMedCrossRefGoogle Scholar
  106. 106.
    McLane MA, Kuchar MA, Brando C, Santoli D, Paquette-Straub CA, Miele ME (2001) New insights on disintegrin-receptor interactions: eristostatin and melanoma cells. Haemostasis 31:177–182PubMedGoogle Scholar
  107. 107.
    McLane MA, Joerger T, Mahmoud A (2008) Disintegrins in health and disease. Front Biosci 13:6617–6637PubMedCrossRefGoogle Scholar
  108. 108.
    Da Silva M, Lucena S, Aguilar I, Rodriguez-Acosta A, Salazar AM, Sanchez EE, Giron ME, Carvajal Z, Arocha-Pinango CL, Guerrero B (2009) Anti-platelet effect of cumanastatin 1, a disintegrin isolated from venom of South American Crotalus rattlesnake. Thromb Res 123:731–739PubMedCrossRefGoogle Scholar
  109. 109.
    Sanchez EE, Rodriguez-Acosta A, Palomar R, Lucena SE, Bashir S, Soto JG, Perez JC (2009) Colombistatin: a disintegrin isolated from the venom of the South American snake (Bothrops colombiensis) that effectively inhibits platelet aggregation and SK-Mel-28 cell adhesion. Arch Toxicol 83:271–279PubMedCrossRefGoogle Scholar
  110. 110.
    Humphries JD, Askari JA, Zhang XP, Takada Y, Humphries MJ, Mould AP (2000) Molecular basis of ligand recognition by integrin alpha5beta 1. II: specificity of arg-gly-Asp binding is determined by Trp157 OF THE alpha subunit. J Biol Chem 275:20337–20345PubMedCrossRefGoogle Scholar
  111. 111.
    Lazarus RA, McDowell RS (1993) Structural and functional aspects of RGD-containing protein antagonists of glycoprotein IIb-IIIa. Curr Opin Biotechnol 4:438–445PubMedCrossRefGoogle Scholar
  112. 112.
    Lu X, Davies J, Lu D, Xia M, Wattam B, Shang D, Sun Y, Scully M, Kakkar V (2006) The effect of the single substitution of arginine within the RGD tripeptide motif of a modified neurotoxin dendroaspin on its activity of platelet aggregation and cell adhesion. Cell Commun Adhes 13:171–183PubMedCrossRefGoogle Scholar
  113. 113.
    Sessions BR, Aston KI, Davis AP, Pate BJ, White KL (2006) Effects of amino acid substitutions in and around the arginine-glycine-aspartic acid (RGD) sequence on fertilization and parthenogenetic development in mature bovine oocytes. Mol Reprod Dev 73:651–657PubMedCrossRefGoogle Scholar
  114. 114.
    Kini RM, Rao VS, Joseph JS (2001) Procoagulant proteins from snake venoms. Haemostasis 31:218–224PubMedGoogle Scholar
  115. 115.
    Rao VS, Kini RM (2002) Pseutarin C, a prothrombin activator from Pseudonaja textilis venom: its structural and functional similarity to mammalian coagulation factor Xa-Va complex. Thromb Haemost 88:611–619PubMedGoogle Scholar
  116. 116.
    Jin Y, Lee WH, Zeng L, Zhang Y (2007) Molecular characterization of l-amino acid oxidase from king cobra venom. Toxicon 50:479–489PubMedCrossRefGoogle Scholar
  117. 117.
    Zhang L, Wu WT (2008) Isolation and characterization of ACTX-6: a cytotoxic l-amino acid oxidase from Agkistrodon acutus snake venom. Nat Prod Res 22:554–563PubMedCrossRefGoogle Scholar
  118. 118.
    Braga MD, Martins AM, Amora DN, de Menezes DB, Toyama MH, Toyama DO, Marangoni S, Alves CD, Barbosa PS, de Sousa AR, Fonteles MC, Monteiro HS (2008) Purification and biological effects of l-amino acid oxidase isolated from Bothrops insularis venom. Toxicon 51:199–207PubMedCrossRefGoogle Scholar
  119. 119.
    Toyama MH, Toyama DO, Passero LF, Laurenti MD, Corbett CE, Tomokane TY, Fonseca FV, Antunes E, Joazeiro PP, Beriam LO, Martins MA, Monteiro HS, Fonteles MC (2006) Isolation of a new l-amino acid oxidase from Crotalus durissus cascavella venom. Toxicon 47:47–57PubMedCrossRefGoogle Scholar
  120. 120.
    Samel M, Vija H, Ronnholm G, Siigur J, Kalkkinen N, Siigur E (2006) Isolation and characterization of an apoptotic and platelet aggregation inhibiting l-amino acid oxidase from Vipera berus berus (common viper) venom. Biochim Biophys Acta 1764:707–714PubMedGoogle Scholar
  121. 121.
    Zhang YJ, Wang JH, Lee WH, Wang Q, Liu H, Zheng YT, Zhang Y (2003) Molecular characterization of Trimeresurus stejnegeri venom l-amino acid oxidase with potential anti-HIV activity. Biochem Biophys Res Commun 309:598–604PubMedCrossRefGoogle Scholar
  122. 122.
    Lu QM, Wei Q, Jin Y, Wei JF, Wang WY, Xiong YL (2002) l-amino acid oxidase from Trimeresurus jerdonii snake venom: purification, characterization, platelet aggregation-inducing and antibacterial effects. J Nat Toxins 11:345–352PubMedGoogle Scholar
  123. 123.
    Ali SA, Stoeva S, Abbasi A, Alam JM, Kayed R, Faigle M, Neumeister B, Voelter W (2000) Isolation, structural, and functional characterization of an apoptosis-inducing l-amino acid oxidase from leaf-nosed viper (Eristocophis macmahoni) snake venom. Arch Biochem Biophys 384:216–226PubMedCrossRefGoogle Scholar
  124. 124.
    Tan NH, Swaminathan S (1992) Purification and properties of the l-amino acid oxidase from monocellate cobra (Naja naja kaouthia) venom. Int J Biochem 24:967–973PubMedCrossRefGoogle Scholar
  125. 125.
    Rodrigues RS, da Silva JF, Boldrini-Franca J, Fonseca FP, Otaviano AR, Henrique-Silva F, Hamaguchi A, Magro AJ, Braz AS, Dos Santos JI, Homsi-Brandeburgo MI, Fontes MR, Fuly AL, Soares AM, Rodrigues VM (2008) Structural and functional properties of Bp-LAAO, a new l-amino acid oxidase isolated from Bothrops pauloensis snake venom. Biochimie 91:490–501CrossRefGoogle Scholar
  126. 126.
    Pawelek PD, Cheah J, Coulombe R, Macheroux P, Ghisla S, Vrielink A (2000) The structure of l-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site. EMBO J 19:4204–4215PubMedCrossRefGoogle Scholar
  127. 127.
    Torii S, Yamane K, Mashima T, Haga N, Yamamoto K, Fox JW, Naito M, Tsuruo T (2000) Molecular cloning and functional analysis of apoxin I, a snake venom-derived apoptosis-inducing factor with l-amino acid oxidase activity. Biochemistry 39:3197–3205PubMedCrossRefGoogle Scholar
  128. 128.
    Du XY, Clemetson KJ (2002) Snake venom l-amino acid oxidases. Toxicon 40:659–665PubMedCrossRefGoogle Scholar
  129. 129.
    Geyer A, Fitzpatrick TB, Pawelek PD, Kitzing K, Vrielink A, Ghisla S, Macheroux P (2001) Structure and characterization of the glycan moiety of l-amino-acid oxidase from the Malayan pit viper Calloselasma rhodostoma. Eur J Biochem 268:4044–4053PubMedCrossRefGoogle Scholar
  130. 130.
    Suhr SM, Kim DS (1996) Identification of the snake venom substance that induces apoptosis. Biochem Biophys Res Commun 224:134–139PubMedCrossRefGoogle Scholar
  131. 131.
    Vieira Santos MM, Sant’ana CD, Giglio JR, da Silva RJ, Sampaio SV, Soares AM, Fecchio D (2008) Antitumoral effect of an l-amino acid oxidase isolated from Bothrops jararaca Snake Venom. Basic Clin. Pharmacol Toxicol 102:533–542Google Scholar
  132. 132.
    Tonismagi K, Samel M, Trummal K, Ronnholm G, Siigur J, Kalkkinen N, Siigur E (2006) l-amino acid oxidase from Vipera lebetina venom: isolation, characterization, effects on platelets and bacteria. Toxicon 48:227–237PubMedCrossRefGoogle Scholar
  133. 133.
    Souza DH, Eugenio LM, Fletcher JE, Jiang MS, Garratt RC, Oliva G, Selistre-de-Araujo HS (1999) Isolation and structural characterization of a cytotoxic l-amino acid oxidase from Agkistrodon contortrix laticinctus snake venom: preliminary crystallographic data. Arch Biochem Biophys 368:285–290PubMedCrossRefGoogle Scholar
  134. 134.
    Clemetson KJ, Morita T, Kini RM (2009) Scientific and standardization committee communications: classification and nomenclature of snake venom C-type lectins and related proteins. J Thromb Haemost 7(2):360PubMedCrossRefGoogle Scholar
  135. 135.
    Weis WI, Taylor ME, Drickamer K (1998) The C-type lectin superfamily in the immune system. Immunol Rev 163:19–34PubMedCrossRefGoogle Scholar
  136. 136.
    Hirabayashi J, Kusunoki T, Kasai K (1991) Complete primary structure of a galactose-specific lectin from the venom of the rattlesnake Crotalus atrox. Homologies with Ca2+-dependent-type lectins. J Biol Chem 266:2320–2326PubMedGoogle Scholar
  137. 137.
    Lin LP, Lin Q, Wang YQ (2007) Cloning, expression and characterization of two C-type lectins from the venom gland of Bungarus multicinctus. Toxicon 50:411–419PubMedCrossRefGoogle Scholar
  138. 138.
    Clemetson KJ, Navdaev A, Dormann D, Du XY, Clemetson JM (2001) Multifunctional snake C-type lectins affecting platelets. Haemostasis 31:148–154PubMedGoogle Scholar
  139. 139.
    Clemetson KJ, Polgar J, Clemetson JM (1998) Snake venom C-type lectins as tools in platelet research. Platelets 9:165–169PubMedCrossRefGoogle Scholar
  140. 140.
    Ogawa T, Chijiwa T, Oda-Ueda N, Ohno M (2005) Molecular diversity and accelerated evolution of C-type lectin-like proteins from snake venom. Toxicon 45:1–14PubMedCrossRefGoogle Scholar
  141. 141.
    Ozeki Y, Matsui T, Hamako J, Suzuki M, Fujimura Y, Yoshida E, Nishida S, Titani K (1994) C-type galactoside-binding lectin from Bothrops jararaca venom: comparison of its structure and function with those of botrocetin. Arch Biochem Biophys 308:306–310PubMedCrossRefGoogle Scholar
  142. 142.
    Aragon-Ortiz F, Mentele R, Auerswald EA (1996) Amino acid sequence of a lectin-like protein from Lachesis muta stenophyrs venom. Toxicon 34:763–769PubMedCrossRefGoogle Scholar
  143. 143.
    Xu Q, Wu XF, Xia QC, Wang KY (1999) Cloning of a galactose-binding lectin from the venom of Trimeresurus stejnegeri. Biochem J 341(Pt 3):733–737PubMedCrossRefGoogle Scholar
  144. 144.
    Hamako J, Suzuki Y, Hayashi N, Kimura M, Ozeki Y, Hashimoto K, Matsui T (2007) Amino acid sequence and characterization of C-type lectin purified from the snake venom of Crotalus ruber. Comp Biochem Physiol B Biochem Mol Biol 146:299–306PubMedCrossRefGoogle Scholar
  145. 145.
    Drickamer K (1993) Recognition of complex carbohydrates by Ca2+-dependent animal lectins. Biochem Soc Trans 21:456–459PubMedGoogle Scholar
  146. 146.
    Walker JR, Nagar B, Young NM, Hirama T, Rini JM (2004) X-ray crystal structure of a galactose-specific C-type lectin possessing a novel decameric quaternary structure. Biochemistry 43:3783–3792PubMedCrossRefGoogle Scholar
  147. 147.
    Gartner TK, Ogilvie ML (1984) Isolation and characterization of three Ca2+-dependent beta-galactoside-specific lectins from snake venoms. Biochem J 224:301–307PubMedGoogle Scholar
  148. 148.
    Ogilvie ML, Byl JW, Gartner TK (1989) Platelet-aggregation is stimulated by lactose-inhibitable snake venom lectins. Thromb Haemost 62:704–707PubMedGoogle Scholar
  149. 149.
    Morita T (2004) C-type lectin-related proteins from snake venoms. Curr Drug Targets Cardiovasc Haematol Disord 4:357–373PubMedCrossRefGoogle Scholar
  150. 150.
    Atoda H, Morita T (1989) A novel blood coagulation factor IX/factor X-binding protein with anticoagulant activity from the venom of Trimeresurus flavoviridis (Habu snake): isolation and characterization. J Biochem (Tokyo) 106:808–813Google Scholar
  151. 151.
    Atoda H, Hyuga M, Morita T (1991) The primary structure of coagulation factor IX/factor X-binding protein isolated from the venom of Trimeresurus flavoviridis. Homology with asialoglycoprotein receptors, proteoglycan core protein, tetranectin, and lymphocyte Fc epsilon receptor for immunoglobulin E. J Biol Chem 266:14903–14911PubMedGoogle Scholar
  152. 152.
    Zingali RB, Jandrot-Perrus M, Guillin MC, Bon C (1993) Bothrojaracin, a new thrombin inhibitor isolated from Bothrops jararaca venom: characterization and mechanism of thrombin inhibition. Biochemistry 32:10794–10802PubMedCrossRefGoogle Scholar
  153. 153.
    Zingali RB, Ferreira MS, Assafim M, Frattani FS, Monteiro RQ (2005) Bothrojaracin, a Bothrops jararaca snake venom-derived (pro)thrombin inhibitor, as an anti-thrombotic molecule. Pathophysiol Haemost Thromb 34:160–163PubMedCrossRefGoogle Scholar
  154. 154.
    Arocas V, Zingali RB, Guillin MC, Bon C, Jandrot-Perrus M (1996) Bothrojaracin: a potent two-site-directed thrombin inhibitor. Biochemistry 35:9083–9089PubMedCrossRefGoogle Scholar
  155. 155.
    Li WF, Chen L, Li XM, Liu J (2005) A C-type lectin-like protein from Agkistrodon acutus venom binds to both platelet glycoprotein Ib and coagulation factor IX/factor X. Biochem Biophys Res Commun 332:904–912PubMedCrossRefGoogle Scholar
  156. 156.
    Atoda H, Morita T (1993) Arrangement of the disulfide bridges in a blood coagulation factor IX/factor X-binding protein from the venom of Trimeresurus flavoviridis. J Biochem (Tokyo) 113:159–163Google Scholar
  157. 157.
    Mizuno H, Fujimoto Z, Koizumi M, Kano H, Atoda H, Morita T (1997) Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nat Struct Biol 4:438–441PubMedCrossRefGoogle Scholar
  158. 158.
    Zingali RB, Bianconi ML, Monteiro RQ (2001) Interaction of bothrojaracin with prothrombin. Haemostasis 31:273–278PubMedGoogle Scholar
  159. 159.
    Wang R, Kini RM, Chung MC (1999) Rhodocetin, a novel platelet aggregation inhibitor from the venom of Calloselasma rhodostoma (Malayan pit viper): synergistic and noncovalent interaction between its subunits. Biochemistry 38:7584–7593PubMedCrossRefGoogle Scholar
  160. 160.
    Paaventhan P, Kong C, Joseph JS, Chung MC, Kolatkar PR (2005) Structure of rhodocetin reveals noncovalently bound heterodimer interface. Protein Sci 14:169–175PubMedCrossRefGoogle Scholar
  161. 161.
    Vargaftig BB, Prado-Franceschi J, Chignard M, Lefort J, Marlas G (1980) Activation of guinea-pig platelets induced by convulxin, a substance extracted from the venom of Crotalus durissus cascavella. Eur J Pharmacol 68:451–464PubMedCrossRefGoogle Scholar
  162. 162.
    Francischetti IM, Saliou B, Leduc M, Carlini CR, Hatmi M, Randon J, Faili A, Bon C (1997) Convulxin, a potent platelet-aggregating protein from Crotalus durissus terrificus venom, specifically binds to platelets. Toxicon 35:1217–1228PubMedCrossRefGoogle Scholar
  163. 163.
    Murakami MT, Zela SP, Gava LM, Michelan-Duarte S, Cintra AC, Arni RK (2003) Crystal structure of the platelet activator convulxin, a disulfide-linked alpha4beta4 cyclic tetramer from the venom of Crotalus durissus terrificus. Biochem Biophys Res Commun 310:478–482PubMedCrossRefGoogle Scholar
  164. 164.
    Batuwangala T, Leduc M, Gibbins JM, Bon C, Jones EY (2004) Structure of the snake-venom toxin convulxin. Acta Crystallogr D Biol Crystallogr 60:46–53PubMedCrossRefGoogle Scholar
  165. 165.
    Taniuchi Y, Kawasaki T, Fujimura Y, Suzuki M, Titani K, Sakai Y, Kaku S, Hisamichi N, Satoh N, Takenaka T (1995) Flavocetin-A and -B, two high molecular mass glycoprotein Ib binding proteins with high affinity purified from Trimeresurus flavoviridis venom, inhibit platelet aggregation at high shear stress. Biochim Biophys Acta 1244:331–338Google Scholar
  166. 166.
    Fukuda K, Mizuno H, Atoda H, Morita T (1999) Crystallization and preliminary X-ray studies of flavocetin-A, a platelet glycoprotein Ib-binding protein from the habu snake venom. Acta Crystallogr D Biol Crystallogr 55:1911–1913PubMedCrossRefGoogle Scholar
  167. 167.
    Lee WH, Du XY, Lu QM, Clemetson KJ, Zhang Y (2003) Stejnulxin, a novel snake C-type lectin-like protein from Trimeresurus stejnegeri venom is a potent platelet agonist acting specifically via GPVI. Thromb Haemost 90:662–671PubMedGoogle Scholar
  168. 168.
    Fry BG, Wuster W, Kini RM, Brusic V, Khan A, Venkataraman D, Rooney AP (2003) Molecular evolution and phylogeny of elapid snake venom three-finger toxins. J Mol Evol 57:110–129PubMedCrossRefGoogle Scholar
  169. 169.
    Fry BG, Lumsden NG, Wuster W, Wickramaratna JC, Hodgson WC, Kini RM (2003) Isolation of a neurotoxin (alpha-colubritoxin) from a nonvenomous colubrid: evidence for early origin of venom in snakes. J Mol Evol 57:446–452PubMedCrossRefGoogle Scholar
  170. 170.
    Pawlak J, Mackessy SP, Fry BG, Bhatia M, Mourier G, Fruchart-Gaillard C, Servent D, Menez R, Stura E, Menez A, Kini RM (2006) Denmotoxin: a three-finger toxin from colubrid snake Boiga dendrophila (mangrove catsnake)with bird-specific activity. J Biol Chem 281:29030–29042CrossRefGoogle Scholar
  171. 171.
    Lumsden NG, Fry BG, Ventura S, Kini RM, Hodgson WC (2005) Pharmacological characterisation of a neurotoxin from the venom of Boiga dendrophila (mangrove catsnake). Toxicon 45:329–334PubMedCrossRefGoogle Scholar
  172. 172.
    Junqueira-de-Azevedo IL, Ching AT, Carvalho E, Faria F, Nishiyama MY Jr, Ho PL, Diniz MR (2006) Lachesis muta (Viperidae) cDNAs reveal diverging pit viper molecules and scaffolds typical of cobra (Elapidae) venoms: implications for snake toxin repertoire evolution. Genetics 173:877–889PubMedCrossRefGoogle Scholar
  173. 173.
    Pahari S, Bickford D, Fry BG, Kini RM (2007) Expression pattern of three-finger toxin and phospholipase A2 genes in the venom glands of two sea snakes, Lapemis curtus and Acalyptophis peronii: comparison of evolution of these toxins in land snakes, sea kraits and sea snakes. BMC Evol Biol 7:175PubMedCrossRefGoogle Scholar
  174. 174.
    Menez A (1998) Functional architectures of animal toxins: a clue to drug design? Toxicon 36:1557–1572PubMedCrossRefGoogle Scholar
  175. 175.
    Tsetlin V (1999) Snake venom alpha-neurotoxins and other ‘three-finger’ proteins. Eur J Biochem 264:281–286PubMedCrossRefGoogle Scholar
  176. 176.
    Kini RM (2002) Molecular moulds with multiple missions: functional sites in three-finger toxins. Clin Exp Pharmacol Physiol 29:815–822PubMedCrossRefGoogle Scholar
  177. 177.
    Pawlak J, Mackessy SP, Fry BG, Bhatia M, Mourier G, Fruchart-Gaillard C, Servent D, Menez R, Stura E, Menez A, Kini RM (2006) Denmotoxin: a three-finger toxin from colubrid snake Boiga dendrophila (mangrove catsnake) with bird-specific activity. J Biol ChemGoogle Scholar
  178. 178.
    Rajagopalan N, Pung YF, Zhu YZ, Wong PT, Kumar PP, Kini RM (2007) {beta}-Cardiotoxin: a new three-finger toxin from Ophiophagus hannah (king cobra) venom with beta-blocker activity. FASEB J 21:3685–3695PubMedCrossRefGoogle Scholar
  179. 179.
    Pawlak J, Mackessy SP, Sixberry NM, Stura EA, Le Du MH, Menez R, Foo CS, Menez A, Nirthanan S, Kini RM (2008) Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity. FASEB J 23:534–545PubMedCrossRefGoogle Scholar
  180. 180.
    Pawlak J, Mackessy SP, Fry BG, Bhatia M, Mourier G, Fruchart-Gaillard C, Servent D, Menez R, Stura E, Menez A, Kini RM (2006) Denmotoxin, a three-finger toxin from the colubrid snake Boiga dendrophila (Mangrove Catsnake) with bird-specific activity. J Biol Chem 281:29030–29041PubMedCrossRefGoogle Scholar
  181. 181.
    Osipov AV, Kasheverov IE, Makarova YV, Starkov VG, Vorontsova OV, Ziganshin RK, Andreeva TV, Serebryakova MV, Benoit A, Hogg RC, Bertrand D, Tsetlin VI, Utkin YN (2008) Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification. J Biol Chem 283:14571–14580PubMedCrossRefGoogle Scholar
  182. 182.
    Chiappinelli VA (1983) Kappa-bungarotoxin: a probe for the neuronal nicotinic receptor in the avian ciliary ganglion. Brain Res 277:9–22PubMedCrossRefGoogle Scholar
  183. 183.
    Dryer SE, Chiappinelli VA (1983) Kappa-bungarotoxin: an intracellular study demonstrating blockade of neuronal nicotinic receptors by a snake neurotoxin. Brain Res 289:317–321PubMedCrossRefGoogle Scholar
  184. 184.
    Chiappinelli VA, Dryer SE (1984) Nicotinic transmission in sympathetic ganglia: blockade by the snake venom neurotoxin kappa-bungarotoxin. Neurosci Lett 50:239–244PubMedCrossRefGoogle Scholar
  185. 185.
    Chiappinelli VA, Lee JC (1985) Kappa-Bungarotoxin: self-association of a neuronal nicotinic receptor probe. J Biol Chem 260:6182–6186PubMedGoogle Scholar
  186. 186.
    Oswald RE, Sutcliffe MJ, Bamberger M, Loring RH, Braswell E, Dobson CM (1991) Solution structure of neuronal bungarotoxin determined by two-dimensional NMR spectroscopy: sequence-specific assignments, secondary structure, and dimer formation. Biochemistry 30:4901–4909PubMedCrossRefGoogle Scholar
  187. 187.
    Sutcliffe MJ, Dobson CM, Oswald RE (1992) Solution structure of neuronal bungarotoxin determined by two-dimensional NMR spectroscopy: calculation of tertiary structure using systematic homologous model building, dynamical simulated annealing, and restrained molecular dynamics. Biochemistry 31:2962–2970PubMedCrossRefGoogle Scholar
  188. 188.
    Dewan JC, Grant GA, Sacchettini JC (1994) Crystal structure of kappa-bungarotoxin at 2.3-A resolution. Biochemistry 33:13147–13154PubMedCrossRefGoogle Scholar
  189. 189.
    Chiappinelli VA, Weaver WR, McLane KE, Conti-Fine BM, Fiordalisi JJ, Grant GA (1996) Binding of native kappa-neurotoxins and site-directed mutants to nicotinic acetylcholine receptors. Toxicon 34:1243–1256PubMedCrossRefGoogle Scholar
  190. 190.
    Chiappinelli VA, Wolf KM (1989) Kappa-neurotoxins: heterodimer formation between different neuronal nicotinic receptor antagonists. Biochemistry 28:8543–8547PubMedCrossRefGoogle Scholar
  191. 191.
    Joubert FJ, Taljaard N (1979) Snake venoms: the amino-acid sequence of protein S2C4 from Dendroaspis jamesoni kaimosae (Jameson’s mamba) venom. Hoppe Seylers Z Physiol Chem 360(57):1–580Google Scholar
  192. 192.
    Liu Y, Eisenberg D (2002) 3D domain swapping: as domains continue to swap. Protein Sci 11:1285–1299PubMedCrossRefGoogle Scholar
  193. 193.
    Kini RM (2005) The intriguing world of prothrombin activators from snake venom. Toxicon 45:1133–1145PubMedCrossRefGoogle Scholar
  194. 194.
    Montecucco C, Rossetto O, Caccin P, Rigoni M, Carli L, Morbiato L, Muraro L, Paoli M (2008) Different mechanisms of inhibition of nerve terminals by botulinum and snake presynaptic neurotoxins. Toxicon (in press)Google Scholar
  195. 195.
    Shikamoto Y, Morita T, Fujimoto Z, Mizuno H (2003) Crystal structure of Mg2+- and Ca2+-bound Gla domain of factor IX complexed with binding protein. J Biol Chem 278:24090–24094PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  1. 1.Protein Science Laboratory, Department of Biological Sciences, Faculty of ScienceNational University of SingaporeSingaporeSingapore
  2. 2.Department of Molecular Biology and BiotechnologyTezpur UniversityAssamIndia
  3. 3.Department of Biochemistry, Medical College of VirginiaVirginia Commonwealth UniversityRichmondUSA

Personalised recommendations