title: Cholinesterase-like domains in enzymes and structural proteins: functional and evolutionary relationships and identification of a catalytically essential aspartic acid.
abstract: Primary sequences of cholinesterases and related proteins have been systematically compared. The cholinesterase-like domain of these proteins, about 500 amino acids, may fulfill a catalytic and a structural function. We identified an aspartic acid residue that is conserved among esterases and lipases (Asp-397 in Torpedo acetylcholinesterase) but that had not been considered to be involved in the catalytic mechanism. Site-directed mutagenesis demonstrated that this residue is necessary for activity. Analysis of evolutionary relationships shows that the noncatalytic members of the family do not constitute a separate subgroup, suggesting that loss of catalytic activity occurred independently on several occasions, probably from bifunctional molecules. Cholinesterases may thus be involved in cell-cell interactions in addition to the hydrolysis of acetylcholine. This would explain their specific expression in well-defined territories during embryogenesis before the formation of cholinergic synapses and their presence in noncholinergic tissues.
authors.affiliation: Laboratoire de Neurobiologie, Centre National de la Recherche Scientifique Unité Associée 295, Ecole Normale Supérieure, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Krejci
authors.forename: N
authors.initials: N
authors.lastname: Duval
authors.forename: A
authors.initials: A
authors.lastname: Chatonnet
authors.forename: P
authors.initials: P
authors.lastname: Vincens
authors.forename: J
authors.initials: J
authors.lastname: Massoulié
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid; D005075:Biological Evolution; D002802:Cholinesterases / Q000235:genetics* / Q000378:metabolism; D004798:Enzymes / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014101:Torpedo
chemical_list: D004798:Enzymes; D011506:Proteins; D001224:Aspartic Acid; D000110:Acetylcholinesterase; D002802:Cholinesterases