[The in vitro production of three-finger neurotoxins from snake venoms with a high abundance of disulfide bonds. Problems and their solutions]

Bioorg Khim. 2010 Mar-Apr;36(2):149-58. doi: 10.1134/s1068162010020019.
[Article in Russian]

Abstract

alpha-Neurotoxins from snake venom are highly efficient inhibitors of nicotinic acetylcholine receptors (nAChR). These small proteins that have a beta-structural organization attract much interest as a tool for studies of nACh R and as prototypes for the development of new Pharmaceuticals for the treatment of diseases of the nervous system. However, the in vitro production of "three-finger" neurotoxins is complicated by the presence of four or five disulfide bonds that are closely located in their molecules. The present review contains a description of the most frequently used modern approaches for the E. coli expression of recombinant proteins (direct expression, expression as fusions, and secretion) with an emphasis placed on the recombinant production of snake alpha-neurotoxins. The methods of E. coli expression of isotopically labeled neurotoxins are described. The proposed solutions will be of broad interest for the bacterial production of other disulfide-abundant proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Disulfides / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Isotope Labeling
  • Molecular Sequence Data
  • Neurotoxins / biosynthesis*
  • Neurotoxins / chemistry
  • Neurotoxins / genetics
  • Peptide Biosynthesis
  • Peptides / chemical synthesis
  • Protein Conformation
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Snake Venoms / chemistry*

Substances

  • Disulfides
  • Neurotoxins
  • Peptides
  • Recombinant Proteins
  • Snake Venoms