Structure-function relationship of bifunctional scorpion toxin BmBKTx1

Acta Biochim Biophys Sin (Shanghai). 2008 Nov;40(11):955-63. doi: 10.1111/j.1745-7270.2008.00479.x.

Abstract

As the first identified scorpion toxin active on both big conductance Ca2+-activated K+ channels (BK) and small conductance Ca2+-activated K+ channels (SK), BmBKTx1 has been proposed to have two separate functional faces for two targets. To investigate this hypothesis, two double mutants, K21A-Y30A and R9A-K11A, together with wild-type toxin were expressed in Escherichia coli. The recombinant toxins were tested on cockroach BK and rat SK2 channel for functional assay. Mutant K21A-Y30A had a dramatic loss of function on BK but retained its function on SK. Mutant R9A-K11A did not lose function on BK or SK. These data support the two functional-face hypothesis and indicate that the BK face is on the C-terminal beta-sheet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Escherichia coli / genetics
  • Mutation
  • Potassium Channels, Calcium-Activated / drug effects
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Scorpion Venoms / chemistry*
  • Scorpion Venoms / genetics
  • Scorpion Venoms / isolation & purification
  • Scorpion Venoms / pharmacology*
  • Structure-Activity Relationship

Substances

  • BKTx1 protein, Buthus martensi
  • Potassium Channels, Calcium-Activated
  • Recombinant Proteins
  • Scorpion Venoms