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Three-dimensional structure of neurotoxin a from venom of the Philippines sea snake
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RE~/IEWS
and S-carboxymethylation of the purified polypeptide, automated Edman degradation and digestion with trypsin, chymotrypsin and cyanogen bromide were used. The amino acid sequence obtained differs from other snake venom toxins. However, it is possible to group it with other low toxic polypeptides, e.g. 4.9.6. from Dendroaspis viridis ('angusticeps type polypeptides') and with the short neurotoxins of Dendroaspis venoms. FS2 is the third most abundant (4.5 ~ ) substance of black mamba venom, but the biological importance of this and other low toxic polypeptides and their phylogenetic significance remain open for speculation. H.M.
TSERNOGLOU,D. and PETSKO, G. A, (Department of Biochemistry, Wayne State University School of Medicine, Detroit, Michigan, U.S.A.). Three-dimensional structure of neurotoxin a from venom of the Philippines sea snake. Proc. Natn. Acad. Sci. U.S.A. 74, 971 (1977). THE CRYSTAL structure of neurotoxin a from the venom of the Philippines sea snake Laticauda semifasciata has been determined at 2"5 A resolution by X-ray diffraction. The molecule contains 62 amino acids, with a histidine residue at position 26 which distinguishes it from its companion b toxin. These two toxins may be identical to the erabutoxins a and b previously isolated from Japanese sea snake venom by Tamiya and coworkers. 'Neurotoxin a' contains an extended ]3-loop which is believed to contain the residues which contribute to its potency in binding to the nicotinic acetylcholine receptor. The authors postulate that this loop is inserted into a deep cleft or channel in the membrane-bound receptor and that the toxic residues in the loop form an active surface which is complementary to a surface on the receptor. The His 26 residue does not appear to interact with this receptor surface. S.L.F.
SUTHERLAND, S. K. (Department of Immunology, Commonwealth Serum Laboratories, Melbourne, Australia). Serum Reactions. An analysis of commercial antivenoms and the possible role of anticomplementary activity in de novo reactions to antivenoms and antitoxins. Med. J. Australia 1,613 (1977). NINE commercial antivenoms from nine countries were examined for their anticomplementary activity (ACA) in an in vitro system containing complement from guinea-pig serum and sheep red blood cells. All nine were found to exhibit high levels of ACT activity. Additionally, antitoxins of equine origin to the toxins of diptheria, tetanus and gas gangrene were tested in the same system and found to display high ACA activities. These results highlight the possibility that infusion of concentrated heterologous serum proteins such as those in antivenoms and antitoxins may precipitate severe ACA reactions in humans. Because of this possibility, such preparations should always be diluted and infused slowly. S.L.F. STRYDOM, D. J. (Division of Molecular Biochemistry, the National Chemical Research Laboratory of the CSIR, P.O. Box 395, Pretoria, South Africa). Snake venom evolution. S. Afr. J. Sci. 73, 70 (1977). 1N "tHIS brief Research Review, the author suggests that phospholipase A, which evolved from an ancestral ribonuclease-lysozyme-phospholipase, gave rise to presynaptic neurotoxins (e.g. notoxin and [3-bungarotoxin) with slight phospholipase activity. Another phospholipase gene developed a more potent lytic action on cell membranes and formed the basis for the evolution of the cyto- or cardiotoxins. Further changes in one such cytotoxin gene enabled it to bind more specifically to acetylcbolire receFtor protein and thus the short and, later, the long neurotoxins were evolved. The major Froteins in Dendroaspis angusticeps venom and their homologues in other mamba venoms evolved from short neurotoxins which lcst their neurotoxicity, according to the author. P.A.C. EBELING, W. (Department of Entomology, University of California, Los Angeles, California). Urban Entomology. University of California Division of Agricultural Sciences, Berkeley, California (1975). WHEN I sat down to read this book two years ago, I had every intention of polishing it off within a week. The book still sits on my desk, not because I have not read it (and I thoroughly enjoyed reading it) but because it has been of continual help to me in clinical problems involving arthropod injuries and in preparing materials for teaching and public health services.
RE~/IEWS
and S-carboxymethylation of the purified polypeptide, automated Edman degradation and digestion with trypsin, chymotrypsin and cyanogen bromide were used. The amino acid sequence obtained differs from other snake venom toxins. However, it is possible to group it with other low toxic polypeptides, e.g. 4.9.6. from Dendroaspis viridis ('angusticeps type polypeptides') and with the short neurotoxins of Dendroaspis venoms. FS2 is the third most abundant (4.5 ~ ) substance of black mamba venom, but the biological importance of this and other low toxic polypeptides and their phylogenetic significance remain open for speculation. H.M.
TSERNOGLOU,D. and PETSKO, G. A, (Department of Biochemistry, Wayne State University School of Medicine, Detroit, Michigan, U.S.A.). Three-dimensional structure of neurotoxin a from venom of the Philippines sea snake. Proc. Natn. Acad. Sci. U.S.A. 74, 971 (1977). THE CRYSTAL structure of neurotoxin a from the venom of the Philippines sea snake Laticauda semifasciata has been determined at 2"5 A resolution by X-ray diffraction. The molecule contains 62 amino acids, with a histidine residue at position 26 which distinguishes it from its companion b toxin. These two toxins may be identical to the erabutoxins a and b previously isolated from Japanese sea snake venom by Tamiya and coworkers. 'Neurotoxin a' contains an extended ]3-loop which is believed to contain the residues which contribute to its potency in binding to the nicotinic acetylcholine receptor. The authors postulate that this loop is inserted into a deep cleft or channel in the membrane-bound receptor and that the toxic residues in the loop form an active surface which is complementary to a surface on the receptor. The His 26 residue does not appear to interact with this receptor surface. S.L.F.
SUTHERLAND, S. K. (Department of Immunology, Commonwealth Serum Laboratories, Melbourne, Australia). Serum Reactions. An analysis of commercial antivenoms and the possible role of anticomplementary activity in de novo reactions to antivenoms and antitoxins. Med. J. Australia 1,613 (1977). NINE commercial antivenoms from nine countries were examined for their anticomplementary activity (ACA) in an in vitro system containing complement from guinea-pig serum and sheep red blood cells. All nine were found to exhibit high levels of ACT activity. Additionally, antitoxins of equine origin to the toxins of diptheria, tetanus and gas gangrene were tested in the same system and found to display high ACA activities. These results highlight the possibility that infusion of concentrated heterologous serum proteins such as those in antivenoms and antitoxins may precipitate severe ACA reactions in humans. Because of this possibility, such preparations should always be diluted and infused slowly. S.L.F. STRYDOM, D. J. (Division of Molecular Biochemistry, the National Chemical Research Laboratory of the CSIR, P.O. Box 395, Pretoria, South Africa). Snake venom evolution. S. Afr. J. Sci. 73, 70 (1977). 1N "tHIS brief Research Review, the author suggests that phospholipase A, which evolved from an ancestral ribonuclease-lysozyme-phospholipase, gave rise to presynaptic neurotoxins (e.g. notoxin and [3-bungarotoxin) with slight phospholipase activity. Another phospholipase gene developed a more potent lytic action on cell membranes and formed the basis for the evolution of the cyto- or cardiotoxins. Further changes in one such cytotoxin gene enabled it to bind more specifically to acetylcbolire receFtor protein and thus the short and, later, the long neurotoxins were evolved. The major Froteins in Dendroaspis angusticeps venom and their homologues in other mamba venoms evolved from short neurotoxins which lcst their neurotoxicity, according to the author. P.A.C. EBELING, W. (Department of Entomology, University of California, Los Angeles, California). Urban Entomology. University of California Division of Agricultural Sciences, Berkeley, California (1975). WHEN I sat down to read this book two years ago, I had every intention of polishing it off within a week. The book still sits on my desk, not because I have not read it (and I thoroughly enjoyed reading it) but because it has been of continual help to me in clinical problems involving arthropod injuries and in preparing materials for teaching and public health services.