title: A long insertion reverts the functional effect of a substitution in acetylcholinesterase.
abstract: 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.
authors.affiliation: Institute for Technical Biochemistry, Allmandring 31, University of Stuttgart, 70569 Stuttgart, Germany.itbfvi@po.uni-stuttgart.de
authors.forename: F
authors.initials: F
authors.lastname: Villatte
authors.forename: H
authors.initials: H
authors.lastname: Schulze
authors.forename: R D
authors.initials: RD
authors.lastname: Schmid
authors.forename: T T
authors.initials: TT
authors.lastname: Bachmann
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics* / Q000502:physiology; D019943:Amino Acid Substitution; D000818:Animals; D007700:Kinetics; D009154:Mutation; D009559:Nippostrongylus / Q000235:genetics / Q000502:physiology
chemical_list: D000110:Acetylcholinesterase