A long insertion reverts the functional effect of a substitution in acetylcholinesterase

F Villatte, H Schulze, R D Schmid, Till Bachmann

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Proteins are thought to undertake single substitutions, deletions and insertions to explore the fitness landscape. Nevertheless, the ways in which these different kind of mutations act together to alter a protein phenotype remain poorly described. We introduced incrementally the single substitution W290A and a 26 amino acid long insertion at the 297 location in the Nippostrongylus brasiliensis acetylcholinesterase B sequence and analysed in vitro the induced changes in the hydrolysis rate of three hemi-substrates: pirimicarb, paraoxon methyl and omethoate. The substitution decreased the hydrolysis rate of the three hemi-substrates. The insertion did not influence this kinetic alteration induced by the substitution for the former hemi-substrate, but reverted it for the two others. These results show that two different kinds of mutations can interact together to influence the direction of a protein's adaptative walk on the fitness landscape.
Original languageEnglish
Pages (from-to)463-5
Number of pages3
JournalProtein Engineering, Design & Selection (PEDS)
Issue number7
Publication statusPublished - 2003

Keywords / Materials (for Non-textual outputs)

  • Acetylcholinesterase
  • Amino Acid Substitution
  • Animals
  • Kinetics
  • Mutation
  • Nippostrongylus


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