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


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


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

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