Cholinesterase-like domains in enzymes and structural proteins: functional and evolutionary relationships and identification of a catalytically essential aspartic acid

Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6647-51. doi: 10.1073/pnas.88.15.6647.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Amino Acid Sequence
  • Animals
  • Aspartic Acid*
  • Biological Evolution*
  • Cholinesterases / genetics*
  • Cholinesterases / metabolism
  • Enzymes / genetics*
  • Humans
  • Molecular Sequence Data
  • Proteins / genetics*
  • Sequence Homology, Nucleic Acid
  • Torpedo

Substances

  • Enzymes
  • Proteins
  • Aspartic Acid
  • Acetylcholinesterase
  • Cholinesterases