Amino Acid Sequence and Chemical Modification of a Novel .ALPHA.-Neurotoxin (Oh-5) from King Cobra (Ophiophagus hannah) Venom.
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- Lin Shinne-Ren
- School of Chemistry, Kaohsiung Medical College
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- Leu Lei-Fen
- Department of Biochemistry, Kaohsiung Medical College
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- Chang Long-Sen
- Department of Biochemistry, Kaohsiung Medical College
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- Chang Chun-Chang
- Department of Biochemistry, Kaohsiung Medical College
抄録
A novel α-neurotoxin, Oh-5, was isolated from king cobra (Ophiophagus hannah) venom and purified by successive SP-Sephadex C-25 column chromatography and reversed-phase HPLC. The complete sequence of Oh-5 was determined by Edman degradation of peptide fragments generated by endopeptidases, i.e., trypsin, Saccharomyces aureus V8 protease and lysyl endopeptidase. This novel toxin comprises 72 amino acid residues with 10 cysteines. The sequence shows 89% sequence homology with Oh-4, and 60% with Toxins a and b from the same venom. The tyrosine, tryptophan, lysine and arginine residues in Oh-5 were modified with tetranitromethane (TNM), 2-nitrophenylsulfenyl (NPS) chloride, trinitrobenzene sulfonate (TNBS), and p-hydroxyphenylglyoxal (HPG), respectively. Modification of Tyr-4 or Trp-27 did not affect the lethal toxicity at all, while the Tyr-4 and 23 nitrated derivative retained about 50% of the lethality of native toxin. Selective trinitrophenylation of Lys-51 or 69 resulted in a decrease in lethality by 29%, and 50% lethality was retained after modification of Lys-2, 51, and 69. A drastic decrease in lethality to 26% was observed when both Arg-35 and 37 were modified. The neurotoxicity was further decreased when Arg-9 was additionally modified. These results suggest that the aromatic residues, Tyr-4 and Trp-27, are not crucial for the neurotoxicity, whereas the cationic residues are involved in multipoint contact between the toxin molecule and the nicotinic acetylcholine receptor (nAChR). The residues Tyr-23 and Arg-35 and 37 in the central loop of Oh-5 seem to contribute greatly to the neurotoxicity.
収録刊行物
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- The Journal of Biochemistry
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The Journal of Biochemistry 121 (4), 690-695, 1997
The Japanese Biochemical Society
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詳細情報 詳細情報について
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- CRID
- 1570291228197523840
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- NII論文ID
- 130003533161
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- ISSN
- 0021924X
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- 本文言語コード
- en
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- データソース種別
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- CiNii Articles