title: Amino-terminal processing of proteins by N-myristoylation. Substrate specificity of N-myristoyl transferase.
abstract: Using synthetic octapeptides, we examined the amino-terminal sequence requirements for substrate recognition by myristoyl-CoA:protein N-myristoyl transferase (NMT). NMT is absolutely specific for peptides with amino-terminal Gly residues. Peptides with Asn, Gln, Ser, Val, or Leu penultimate to the amino-terminal Gly were substrates, whereas peptides with Asp, D-Asn, Phe, or Tyr at this position were not myristoylated. Peptides with aromatic residues at this position competitively inhibited myristoylation of substrates, introducing the possibility of developing specific in vivo inhibitors of NMT. Peptides having sequences which correspond to those of known N-myristoyl proteins, including p60src, appear to be recognized by a single enzyme, and yeast and murine NMT have identical substrate specificities. The catalytic selectivity of NMT for myristoyl transfer accounts for the remarkable acyl chain specificity of this enzyme.
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D007700:Kinetics; D051379:Mice; D009132:Muscles / Q000201:enzymology; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology; D015688:Oncogene Protein pp60(v-src); D010446:Peptide Fragments / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D000214:Acyl Coenzyme A; D002148:Calmodulin-Binding Proteins; D009227:Myristic Acids; D009842:Oligopeptides; D010446:Peptide Fragments; D012191:Retroviridae Proteins; D019814:Myristic Acid; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase; D015688:Oncogene Protein pp60(v-src)