The structure of myristoyl-CoA:protein N-myristoyltransferase

Rajiv S. Bhatnagar, Klaus Fütterer, Gabriel Waksman, Jeffrey I. Gordon

Research output: Contribution to journalReview articlepeer-review

55 Scopus citations


Protein N-myristoylation is a covalent modification that occurs co-translationally in eukaryotes. Myristate, a rare 14 carbon saturated fatty acid (C14:0), is attached, via an amide linkage, to the N-terminal glycine of a subset of eukaryotic and viral proteins by myristoyl-CoA:protein N-myristoyltransferase (Nmt). Genetic and biochemical studies have established that Nmt is a target for development of a new class of fungicidal drugs. The enzyme is also a potential target for development of antiviral and antineoplastic agents. The structure of Saccharomyces cerevisiae Nmt1p has been determined recently with bound substrate analogs. The Nmt fold resembles the fold of members of the GCN5-related N-acetyltransferase superfamily. The structure reveals how Nmt's myristoyl-CoA and peptide substrates are recognized and bound, and what elements control the enzyme's ordered kinetic mechanism. Acyl transfer occurs through the nucleophilic addition-elimination reaction: an oxyanion hole formed by main chain atoms polarizes the thioester carbonyl and stabilizes the transition state while deprotonation of the ammonium of the Gly acceptor appears to be mediated by Nmt's C-terminal carboxylate. The use of main chain carboxylate atoms as general base catalyst is a novel feature. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)162-172
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number2-3
StatePublished - Nov 23 1999


  • Acyl CoA recognition
  • Acyltransferase
  • Enzyme mechanism
  • GCN5
  • Oxyanion hole
  • Protein N-myristoylation


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