11-(Ethylthio)undecanoic acid. A myristic acid analogue of altered hydrophobicity which is functional for peptide N-myristoylation with wheat germ and yeast acyltransferase

J Biol Chem. 1988 Feb 15;263(5):2127-33.

Abstract

The covalent attachment of myristic acid to the NH2-terminal glycine residue of proteins is catalyzed by the enzyme myristoyl CoA:protein N-myristoyltransferase (NMT). Using synthetic octapeptide substrates we have identified and characterized an NMT activity in wheat germ lysates used for cell-free translation of exogenous mRNAs. C-12 and C-14 fatty acids are efficiently transferred to the peptides by this plant NMT, but C-10 and C-16 fatty acids are not. Glycine is required as the NH2-terminal residue: peptides with an NH2-terminal alanine were not substrates. Peptides with proline, aspartic acid, or tyrosine residues adjacent to the NH2-terminal glycine were also not myristoylated. Serine in the fifth position reduced the peptide's Km up to 4000-fold. We have chemically synthesized a sulfur analogue of myristate, 11-(ethylthio)undecanoic acid. Its CoA ester is as good a substrate as myristoyl-CoA for both wheat germ and yeast NMT. Peptides linked to 11-(ethylthio)undecanoic acid are less hydrophobic than the corresponding myristoylpeptides. 11-(Ethylthio)-undecanoic acid may, therefore, help define the role of myristic acid in targeting of acyl proteins within cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / metabolism*
  • Chromatography, High Pressure Liquid
  • Fatty Acids / metabolism*
  • Kinetics
  • Oncogene Protein pp60(v-src)
  • Peptides / metabolism
  • Protein Biosynthesis
  • RNA, Messenger / metabolism
  • Retroviridae Proteins / genetics
  • Saccharomyces cerevisiae / enzymology
  • Substrate Specificity
  • Triticum

Substances

  • Fatty Acids
  • Peptides
  • RNA, Messenger
  • Retroviridae Proteins
  • 11-(ethylthio)undecanoic acid
  • Acyltransferases
  • glycylpeptide N-tetradecanoyltransferase
  • Oncogene Protein pp60(v-src)