Snake Venoms pp 213-257 | Cite as

The Three-Dimensional Structure of Postsynaptic Snake Neurotoxins: Consideration of Structure and Function

  • Barbara W. Low
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 52)


The structural expression of function in biological systems is three-dimensional at all levels of resolutions. In interactions between single molecules, for examples, between deoxyhemoglobin and oxygen, or between enzymes and their substrates, the relative geometric positioning of the specific groups of atoms and their distances from each other is critical as measured in Ångstroms (10−8cm; 0.10nm) or tenths of an Ångstrom. The proper articulation of the wrist depends on the size, shape, orientation, and placement of more gross segments, but the principle holds. Furthermore, interactions at all levels from macroscopic to molecular are recognized as frequently involving favorable geometric repositioning; that is, in molecular interactions, shifts from inactive to active conformations as, for example, the 12 Å shift of the phenolic OH which accompanies the flip-over swing of Tyr 248 in carboxypeptidase A when substrate binds to enzyme (Quiocho and Lipscomb, 1971). These shifts may be induced in one molecule by the proximity of another with which it interacts.


Reactive Site Snake Venom Disulfide Linkage Optical Rotatory Dispersion Conservative Substitution 
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  1. Arai, H., Tamiya, N., Toshioka, S., Shinonaga, S., Kano, R.: Studies on Sea-Snake Venoms. I. Protein nature of the neurotoxin component. J. Biochem. (Tokyo) 56, 568–571 (1964)Google Scholar
  2. Arseniev, A.S., Balashova, T.A., Utkin, Y.N., Tsetlin, V.I., Bystrov, V.F., Ivanov, V.T., Ovchinnikov, Y. A.: Proton NMR study of the conformation of neurotoxin II from middleasian cobra Naja naja oxiana venom. Europ. J. Biochem. 71, 595–606 (1976)PubMedCrossRefGoogle Scholar
  3. Balls, A. K., Jansen, E. F.: Stoichiometric inhibition of chymotrypsin. Advanc. Enzymol. 13, 321–343 (1952)Google Scholar
  4. Banks, B.C.E., Miledi, R., Shipolini, R.A.: The primary sequences and neuromuscular effects of three neurotoxic polypeptides from the venom of Dendroaspis viridis. Europ. J. Biochem. 45, 457–468 (1974)PubMedCrossRefGoogle Scholar
  5. Bartels, E., Rosenberry, T.L.: Snake neurotoxins: effect of disulfide reduction on interaction with electroplax. Science 174, 1236–1237 (1971)PubMedCrossRefGoogle Scholar
  6. Biesecker, G.: Molecular properties of the cholinergic receptor purified from Electrophorus electrica. Biochemistry 12, 4403–4409 (1973)PubMedCrossRefGoogle Scholar
  7. Botes, D.P.: Snake venom toxins. The reactivity of the disulphide bonds of Naja nivea toxina. Biochim. biophys. Acta (Amst.) 359, 242–247 (1974)Google Scholar
  8. Chang, C. C., Lee, C. Y.: Isolation of neurotoxins from the venom of Bungarus multicinctus and their modes of neuromuscular blocking action. Arch. int. Pharmacodyn. 144, 241–257 (1963)PubMedGoogle Scholar
  9. Chang, C.C., Yang, C.C., Hamaguchi, K., Nakai, K., Hayashi, K.: Studies on the status of tyrosyl residues in cobrotoxin. Biochim. biophys. Acta (Amst.) 236, 164–173 (1971 a)Google Scholar
  10. Chang, C. C., Yang, C. C., Nakai, K., Hayashi, K.: Studies on the status of free amino and carboxyl groups in cobrotoxin. Biochim. biophys. Acta (Amst.) 251, 334–344 (1971 b)Google Scholar
  11. Changeux, J.-P., Kasai, M., Lee, C.Y.: Use of a snake venom toxin to characterize the cholinergic receptor protein. Proc. nat. Acad. Sci. (Wash.) 67, 1241–1247 (1970)CrossRefGoogle Scholar
  12. Changeux, J.-P., Benedetti, L., Bourgeois, J.-P., Brisson, A., Cartaud, J., Devaux, P., Grunhagen, H., Moreau, M., Popot, J.-L., Sobel, A., Weber, M.: Some structural properties of the cholinergic receptor protein in its membrane environment relevant to its function as a pharmacological receptor. In: Cold Spring Harbor Symposia on Quantitative Biology, The Synapse, Vol. XI, pp. 211–230. Pub. Cold Spring Harbor, N.Y.: Cold Spring Harbor Lab. 1975Google Scholar
  13. Changeux, J.-P., Meunier, J. C., Huchet, M.: Studies on the cholinergic receptor protein of Electrophorus Electricus. I. An assay in vitro for the cholinergic receptor site and solubilization of the receptor protein from electric tissue. J. molec. Pharmacol. 7, 538–553 (1971)Google Scholar
  14. Chicheportiche, R., Rochat, C., Sampieri, F., Lazdunski, M.: Structure-function relationships of neurotoxins isolated from Naja haje venom. Physicochemical properties and identification of the active site. Biochemistry 11, 1681–1691 (1972)PubMedCrossRefGoogle Scholar
  15. Chou, P. Y., Fasman, G.D.: Conformational parameters for amino acids in helical, β-sheet, and random coil regions calculated from proteins. Biochemistry 13, 211–222 (1974 a)PubMedCrossRefGoogle Scholar
  16. Chou, P.Y., Fasman, G.D.: Prediction of protein conformation. Biochemistry 13, 222–245 (1974b)PubMedCrossRefGoogle Scholar
  17. Christensen, P.A.: South African Snake Venoms and Antivenoms. Johannesburg: The South African Inst. Med. Res. 1955Google Scholar
  18. Crane, G.A., Rosen, L.S., Low, B.W.: Unpublished studies (1977)Google Scholar
  19. Dickerson, R.E., Geis, I.: The Structure and Action of Proteins. New York: Harper & Row 1969Google Scholar
  20. Eaker, D.: Structure and Function of Snake Venom toxins. In: Walter, R., Meienhofer, J. (Eds.): Peptides: Chemistry, Structure and Biology. Proc. 4th Am. Peptide Symposium, pp. 17–30. Ann Arbor, Michigan: Ann Arbor—Science Publisher’s Inc. 1975Google Scholar
  21. Eldefrawi, M.E., Eldefrawi, A.T., Shamoo, A.E.: Molecular and functional properties of the ace-tylcholine-receptor. Ann. N.Y. Acad. Sci. 264, 183–202 (1975)PubMedCrossRefGoogle Scholar
  22. Gabel, D., Rasse, D., Scheraga, H. A.: Search for low-energy conformations of a neurotoxic protein by means of predictive rules, tests for hard-sphere overlaps, and energy minimization. Int. J. Peptide Res. 8, (3), 237–252 (1976)CrossRefGoogle Scholar
  23. Hall, Z.W.: Release of neurotransmitters and their interaction with receptors. Ann. Rev. Biochem. 41, 925–952 (1972)PubMedCrossRefGoogle Scholar
  24. Hamaguchi, K., Ikeda, K., Lee, C.Y.: Optical rotatory dispersion and circular dichroism of neurotoxins isolated from the venom of Bungarus multicinctus. J. Biochem. (Tokyo) 64, 503–506 (1968)Google Scholar
  25. Harada, I., Takamatsu, T., Shimanouchi, T., Miyazawa, T., Tamiya, N.: Raman spectra of some neurotoxins and denatured neurotoxins in relation to structure and toxicities. J. Phys. Chem. 80, 1153–1156 (1976)CrossRefGoogle Scholar
  26. Homma, M., Okonogi, T., Mishima, S.: Studies on sea snake venoms. I. Biological toxicities of venoms possessed by three species of sea snake captured in coastal water of Amami Oshima. Gunma J. med. Sci. 13, 283–296 (1964)Google Scholar
  27. Hori, H., Tamiya, N.: Preparation and activity of guanidinated or acetylated erabutoxins. Biochem. J. 153, 217–222 (1976)PubMedGoogle Scholar
  28. Huang, J.S., Liu, S.S., Ling, K.H., Chang, C.C., Yang, C.C.: Iodination of cobrotoxin. Toxicon 11, 39–45 (1973)PubMedCrossRefGoogle Scholar
  29. Ishikawa, Y., Menez, A., Hori, H., Yoshida, H., Tamiya, N.: Structure of snake toxins and their affinity to the acetylcholine receptor of fish electric organ. Toxicon 15, 477–488 (1977)PubMedCrossRefGoogle Scholar
  30. Karlin, A.: Current Problems in Acetylcholine Receptor Research. In: Rowland, L.F.: Pathogenesis of Human Muscular Dystrophies. Amsterdam: Excerpta Medica, 1977, pp.73–84Google Scholar
  31. Karlin, A., Weill, C., McNamee, M., Valderrama, R.: Facets of the structures of acetylcholine receptors from Electrophorus and Torpedo. In: Cold Spring Harbor Symposia on Quantitative Biology. The Synapse. Vol. XL, pp. 203–210. N.Y. Cold Spring Harbor Lab.: Pub. Cold Spring Harbor, 1975Google Scholar
  32. Karlsson, E., Arnberg, H., Eaker, D.: Isolation of the principal neurotoxins of two Naja naja subspecies. Europ. J. Biochem. 21, 1–16 (1971)PubMedCrossRefGoogle Scholar
  33. Karlsson, E., Eaker, D.: Chemical modifications of the postsynaptic Naja naja neurotoxins. J. Formosan med. Ass. 71, 358–371 (1972)Google Scholar
  34. Karlsson, E., Fohlman, J., Groth, M.: Purification of the acetylcholine receptor from the electric organ of Torpedo marmorata. Bull. Inst. Pasteur 74, 11–22 (1976)Google Scholar
  35. Karlsson, E., Sundelin, J.: Nitration of tyrosine in three cobra neurotoxins. Toxicon 14, 295–306 (1976)PubMedCrossRefGoogle Scholar
  36. Klett, R.P., Fulpius, B.W., Cooper, D., Smith, M., Reich, E., Possani, L.D.: The acetylcholine receptor. J. biol. Chem. 248, 6841–6853 (1973)PubMedGoogle Scholar
  37. Lee, C.Y.: Chemistry and pharmacology of polypeptide toxins in snake venoms. Ann. Rev. Pharmacol. 12, 265–286 (1972)PubMedCrossRefGoogle Scholar
  38. Low, B.W.: The three dimensional structure of erabutoxin b neurotoxic protein. The Fifth International Symposium of Animal, Plant, and Microbial Toxins of the International Society on Toxinology in San Jose, Costa Rica 1976 a.Google Scholar
  39. Low, B.W.: Unpublished studies (1976b)Google Scholar
  40. Low, B.W., Potter, R., Jackson, R.B., Tamiya, N., Sato, S.: X-ray crystallographic study of the erabutoxins and of a diiodo derivative. J. biol. Chem. 246, 4366–4368 (1971)PubMedGoogle Scholar
  41. Low, B.W., Preston, H.S., Sato, A., Rosen, L.S., Searl, J.E., Rudko, A.D., Richardson, J.S.: Three dimensional structure of erabutoxin b neurotoxic protein: Inhibitor of acetylcholine receptor. Proc. nat. Acad. Sci. (Wash.) 73, 2991–2994 (1976 a)CrossRefGoogle Scholar
  42. Low, B. W., Preston, H. S., Sato, A., Rosen, L., Richardson, J. S.: Unpublished studies (1976 b)Google Scholar
  43. Maeda, N., Takagi, K., Tamiya, N., Chen, Y.-M., Lee, C.Y.: The isolation of an easily reversible post-synaptic toxin from the venom of a sea snake, Laticauda semifasciata. Biochem. J. 141, 383–387 (1974)PubMedGoogle Scholar
  44. Maeda, N., Tamiya, N.: The primary structure of the toxin Laticauda semifasciata III, a weak and reversible acting neurotoxin from the venom of a sea snake, Laticauda semifasciata. Biochem. J. 141, 389–400 (1974)PubMedGoogle Scholar
  45. Maeda, N., Tamiya, N.: Correction of partial amino acid sequence of erabutoxins. Biochem. J. 167, 289–291 (1977)PubMedGoogle Scholar
  46. Maelicke, A., Reich, E.: On the interaction between cobra α-neurotoxin and the acetylcholine receptor. In: Cold Spring Harbor Symposia on Quantitative Biology, The Synapse, Vol. XL, pp. 231–235. N.Y. Cold Spring Harbor Lab.: Pub. Cold Spring Harbor 1975Google Scholar
  47. Mebs, D., Narita, K., Iwanaga, S., Samejima, Y., Lee, C.Y.: Purification, properties, and amino acid sequence of α-bungarotoxin from the venom of Bungarus multicinctus. Hoppe-Seylers Z. physiol. Chem. 353, 243–262 (1972)CrossRefGoogle Scholar
  48. Mebs, D., Narita, K., Lee, C.Y.: Amino acid sequence of α-bungarotoxin from the venom of Bungarus multicinctus. Biochem. Biophys. Res. Commun. 44, 711–716 (1971)PubMedCrossRefGoogle Scholar
  49. Menez, A., Bouet, F., Fromageot, P., Tamiya, N.: On the role of tyrosyl and tryptophanyl residues in the conformation of two snake neurotoxins. Bull. Inst. Pasteur 74, 57–64 (1976 a)Google Scholar
  50. Menez, A., Boquet, P., Tamiya, N., Fromageot, P.: Conformational changes in two neurotoxic proteins from snake venoms. Biochim. biophys. Acta (Amst.) 453, 121–132 (1976 b)Google Scholar
  51. Meunier, J.-C., Sealock, R., Olsen, R., Changeux, J.-P.: Purification and properties of the cholinergic receptor protein from Electrophorus electricus electric tissue. Europ. J. Biochem. 45, 371–394 (1974)PubMedCrossRefGoogle Scholar
  52. Miledi, R., Molinof, P., Potter, L.T.: Isolation of the cholinergic receptor protein of Torpedo electric tissue. Nature (Lond.) 229, 554–557 (1971)CrossRefGoogle Scholar
  53. Nakai, K., Sasaki, T., Hayashi, K.: Amino acid sequence of toxin A from the venom of the Indian cobra (Naja naja). Biochem. Biophys. Res. Commun. 41, 893–897 (1971)CrossRefGoogle Scholar
  54. Ohta, M., Hayashi, K.: Chemical modification of the tyrosine residue in toxin B from the venom of the Indian cobra Naja naja. Biochem. Biophys. Res. Commun. 56, 981–987 (1974)CrossRefGoogle Scholar
  55. Preston, H.S., Kay, J., Sato, A., Low, B.W., Tamiya, N.: Crystalline erabutoxinc. Toxicon 13, 273–275 (1975)PubMedCrossRefGoogle Scholar
  56. Quiocho, F.A., Lipscomb, W.W.: Carboxypeptidase A: a protein and an enzyme. Advanc. Protein Chem. 25, 1–59 (1971)CrossRefGoogle Scholar
  57. Raftery, M. A., Schmidt, J., Clark, D.G., Wolcott, R.G.: Demonstration of a specific α-bungarotoxin binding component in Electrophorus electricus electroplax membranes. Biochem. biophys. Res. Commun. 45, 1622–1629 (1971)PubMedCrossRefGoogle Scholar
  58. Raftery, M.A., Vandlen, R.L., Reed, K.L., Lee, T.: Characterization of Torpedo californica acetylcholine receptor: Its subunit composition and ligand-binding properties. In: Cold Spring Harbor Symposia on Quantitative Biology, The Synapse, Vol. XL, pp. 193–202. N.Y.: Cold Spring Harbor Lab., Pub. Cold Spring Harbor 1975Google Scholar
  59. Richardson, J.S.: Handedness of crossover connections in β sheets. Proc. nat. Acad. Sci. (Wash.) 73, 2619–2623 (1976)CrossRefGoogle Scholar
  60. Ryden, L., Gabel, D., Eaker, D.: A model of the three-dimensional structure of snake venom neurotoxins based on chemical evidence. Int. J. Peptide Protein Res. 5, 261–273 (1973)CrossRefGoogle Scholar
  61. Sato, A.: The X-Ray Crystallographic Studies on Sea Snake Neurotoxins. Ph.D. Thesis, Dept. of Chemistry, Tohoku Univ. Jpn 1977Google Scholar
  62. Sato, A., Rosen, L.S., Richardson, J.S., Low, B.W.: Unpublished studies (1977)Google Scholar
  63. Sato, N., Tamiya, N., Ikeda, K., Hamaguchi, K.: Unpublished studies (1968)Google Scholar
  64. Sato, S., Abe, T., Tamiya, N.: Binding of iodinated erabutoxin b; A sea snake toxin to the end-plates of the mouse diaphragm. Toxicon 8, 313–314 (1970)PubMedCrossRefGoogle Scholar
  65. Sato, S., Tamiya, N.: Iodination of erabutoxin b: Diiodohistidine formation. J. Biochem. (Tokyo) 68, 867–872 (1970)Google Scholar
  66. Sato, S., Tamiya, N.: The amino acid sequences of erabutoxins, neurotoxic proteins of sea-snake (Laticauda semifasciata) venom. Biochem. J. 122, 453–461 (1971)PubMedGoogle Scholar
  67. Sato, S., Yoshida, H., Abe, H., Tamiya, N.: Properties and biosynthesis of a neurotoxic protein of the venoms of sea snakes Laticauda laticaudata and Laticauda colubrina. Biochem. J. 115, 85–90 (1969)PubMedGoogle Scholar
  68. Serl J.E., Fullerton, W.W., Low, B.W.: X-ray crystallographic study of laticotoxina. J. biol. Chem. 248, 6057–6058 (1973)Google Scholar
  69. Sheu, Y. S.: Influence of diisopropylfluorophosphate on the thrombinlike action of snake venoms. J. Formosan med. Ass. 61, 245–250 (1962)Google Scholar
  70. Shipolini, R.A., Bailey, G.S., Edwardson, J.A., Banks, B.E.C.: Separation and characterization of polypeptide from the venom of Dendroaspis viridis. Europ. J. Biochem. 40, 337–344 (1973)PubMedCrossRefGoogle Scholar
  71. Shü, I.C., Ling, K.H., Yang, C.C.: Study on I131 labeled cobrotoxin. Toxicon 5, 295–301 (1968)PubMedCrossRefGoogle Scholar
  72. Smythies, J.R., Bennington, F., Bradley, R. J., Bridgers, W.F., Morin, R.D., Romine, W.O.: The molecular structure of the receptor-ionophore complex at the neuromuscular junction. J. theor. Biol. 51 (1), 111–126 (1975)PubMedCrossRefGoogle Scholar
  73. Takamatsu, T., Harada, I., Shimanouchi, T., Ohta, M., Hayashi, K.: Raman spectrum of toxin B in relation to structure and toxicity. FEBS Letters 72, (2) 291–294 (1976)PubMedCrossRefGoogle Scholar
  74. Tamiya, N.: Erabutoxins a, b, and c in sea snake Laticauda semifasciata venom. Toxicon 11, 95 – 97 (1973)PubMedCrossRefGoogle Scholar
  75. Tamiya, N., Abe, H.: The isolation, properties and amino acid sequence of erabutoxin c, a minor neurotoxic component of the venom of a sea snake Laticauda semifasciata venom. Biochem. J. 130, 547–555 (1972)PubMedGoogle Scholar
  76. Tamiya, N., Arai, H.: Studies on sea-snake venoms. Crystallization of erabutoxins a and b from Laticauda semifasciata venom. Biochem. J. 99, 624–630 (1966)PubMedGoogle Scholar
  77. Tamiya, N., Takasaki, C.: Detection of erabutoxins in the venom of sea snake Laticauda semifasciata from the Philippines. Biochim. biophys. Acta (Amst.) 532, 199–201 (1978)Google Scholar
  78. Tsernoglou, D., Petsko, G.A.: The crystal structure of a postsynaptic neurotoxin from sea snake at 2.2 Å resolution. FEBS Letters 68(1), 1–4 (1976)PubMedCrossRefGoogle Scholar
  79. Tsetlin, V.I., Mikhaleva, I.I., Myagkova, M. A., Senyavina, L.B., Arseniev, A.S., Ivanov, V.T., Ovchinnikov, Y. A.: Synthetic and conformational studies of the neurotoxins and cytotoxins of snake venom. In: Walter, R., Meienhofer, J. (Eds.): Peptides: Chemistry, Structure and Biology. Proc. 4th Am. Peptide Symposium, pp.935–941. Ann Arbor, Michigan: Ann Arbor-Science Publisher’s Inc., 1975Google Scholar
  80. Tu, A. T., Hong, B., Solie, T.N.: Characterization and chemical modifications of toxins isolated from the venoms of the sea snake Laticauda semifasciata, from Philippines. Biochemistry 10(8), 1295–1304 (1971)PubMedCrossRefGoogle Scholar
  81. Venkatachalam, C. M.: Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers 6, 1425–1436 (1968)PubMedCrossRefGoogle Scholar
  82. Weber, M., Changeux, J.-P.: Binding of Naja nigricollis [3H] α-toxin to membrane fragments from Electrophorus and Torpedo electric organs. II. Effect of cholinergic agonists and antagonists on the binding of the tritiated α-neurotoxin. J. molec. Pharmacol. 10, 15–34 (1974)Google Scholar
  83. Weill, C.L., McNamee, M. G., Karlin, A.: Affinity-labeling of purified acetylcholine receptor from Torpedo californica. Biochem. Biophys. Res. Commun. 61, 997–1003 (1974)PubMedCrossRefGoogle Scholar
  84. Wong, C., Chang, T. W., Lee, T. J., Yang, C.C.: X-ray crystallographic study of cobrotoxin. J. biol. Chem. 247, 608 (1972)PubMedGoogle Scholar
  85. Yang, C.C.: Enzymic hydrolysis and chemical modification of cobrotoxin. Toxicon 3, 19–22 (1964)CrossRefGoogle Scholar
  86. Yang, C.C.: Crystallization and properties of cobrotoxin from Formosan cobra venom. J. biol. Chem. 240, 1616–1618 (1965)PubMedGoogle Scholar
  87. Yang, C. C.: The disulfide bonds of cobrotoxin and their relationship to lethality. Biochim. biophys. Acta (Amst.) 133, 346–355 (1967)Google Scholar
  88. Yang, C.C.: Chemistry and evolution of toxins in snake venoms. Toxicon 12, 1–43 (1974)PubMedCrossRefGoogle Scholar
  89. Yang, C.C., Chang, C.C., Hamaguchi, K., Ikeda, K., Hayashi, K., Suzuki, T.: Optical rotatory dispersion of cobrotoxin. J. Biochem. (Tokyo) 61, 272–274 (1967)Google Scholar
  90. Yang, C.C., Chang, C.C., Hayashi, K., Suzuki, T., Ideka, K., Hamaguchi, K.: Optical rotatory dispersion and circular dichoism of cobrotoxin. Biochim. biophys. Acta (Amst.) 168, 373–376 (1968)Google Scholar
  91. Yang, C.C., Chang, C.C., Liu, I. F.: Studies on the Status of Arginine Residues in Cobrotoxin. 9 th Int. Congr. Biochem. Stockholm. Colloquium D, Abs. p. 455, 1973Google Scholar
  92. Yii, N.T., Lin, T.S., Tu, A. T.: Laser raman scattering of neurotoxins isolated from the venoms of sea snakes Lapemis hardwickii and Enhydrina schistosa. J. biol. Chem. 250, 1782–1785 (1975)Google Scholar

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  • Barbara W. Low

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