Site-directed mutagenesis of the toxin from the Chinese scorpion Buthus martensii Karsch (BmKAS): insight into sites related to analgesic activity

Arch Pharm Res. 2010 Oct;33(10):1633-9. doi: 10.1007/s12272-010-1012-9. Epub 2010 Oct 30.

Abstract

This study utilized the E. coli expression system to investigate the role of amino acid residues in toxin from the Chinese scorpion--Buthus martensii Karsch (BmKAS). To evaluate the extent to which residues of the toxin core contribute to its analgesic activity, ten mutants of BmKAS were obtained by PCR. Using site-directed mutagenesis, all of these residues were substituted with different amino acids. This study represents a thorough mapping and elucidation of the epitopes that form the molecular basis of the toxin's analgesic activity. Our results showed large mutant-dependent differences that emphasize the important roles of the studied residues.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Analgesics, Non-Narcotic / chemistry*
  • Analgesics, Non-Narcotic / pharmacology*
  • Animals
  • Insect Proteins / chemistry*
  • Insect Proteins / genetics
  • Insect Proteins / pharmacology*
  • Mice
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutant Proteins / chemistry
  • Mutant Proteins / isolation & purification
  • Mutant Proteins / pharmacology
  • Neurotoxins / chemistry
  • Neurotoxins / genetics
  • Neurotoxins / pharmacology
  • Pain Measurement
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / pharmacology*
  • Protein Conformation
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Scorpion Venoms / chemistry*
  • Scorpion Venoms / genetics
  • Scorpion Venoms / pharmacology*
  • Scorpions / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship

Substances

  • Analgesics, Non-Narcotic
  • Insect Proteins
  • KAS toxin, Buthus martensi Karsch
  • LqhIT2 insect toxin
  • Mutant Proteins
  • Neurotoxins
  • Peptides
  • Recombinant Proteins
  • Scorpion Venoms