On the Convergent Evolution of Animal Toxins

BgK is a K+ channel-blocking toxin from the sea anemone Bunodosoma granulifera It is a 37-residue protein that adopts a novel fold, as determined by NMR and modeling. An alanine-scanning-based analysis revealed the functional importance of five residues, which include a critical lysine and an aromatic residue separated by 6.6 ± 1.0 Å. The same diad is found in the three known homologous toxins from sea anemones. More strikingly, a similar functional diad is present in all K+ channel-blocking toxins from scorpions, although these toxins adopt a distinct scaffold. Moreover, the functional diads of potassium channel-blocking toxins from sea anemone and scorpions superimpose in the three-dimensional structures. Therefore, toxins that have unrelated structures but similar functions possess conserved key functional residues, organized in an identical topology, suggesting a convergent functional evolution for these small proteins.

• Publication year

  1997

• Venue

  Journal of Biological Chemistry

• Publication date

  1997-02-14

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.1074/jbc.272.7.4302PMID 9020148
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  1994cited by this paper
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  1993cited by this paper
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  1993cited by this paper
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  1992cited by this paper
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  1992cited by this paper
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  1989cited by this paper
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  1988cited by this paper
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  1986cited by this paper
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  1985cited by this paper
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  1985cited by this paper
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  1983cited by this paper
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  1983cited by this paper
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  1982cited by this paper
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