Structure of N-myristoyltransferase with bound myristoylCoA and peptide substrate analogs

Rajiv S. Bhatnagar, Klaus Fütterer, Thalia A. Farazi, Sergey Korolev, Clare L. Murray, Emily Jackson-Machelski, George W. Gokel, Jeffrey I. Gordon, Gabriel Waksman

Research output: Contribution to journalReview articlepeer-review

105 Scopus citations

Abstract

N-myristoyltransferase (Nmt) attaches myristate to the N-terminal glycine of many important eukaryotic and viral proteins. It is a target for anti-fungal and anti-viral therapy. We have determined the structure, to 2.9 Å resolution, of a ternary complex of Saccharomyces cerevisiae Nmt1p with bound myristoylCoA and peptide substrate analogs. The model reveals structural features that define the enzyme's substrate specificities and regulate the ordered binding and release of substrates and products. A novel catalytic mechanism is proposed involving deprotonation of the N-terminal ammonium of a peptide substrate by the enzyme's C-terminal backbone carboxylate.

Original languageEnglish
Pages (from-to)1091-1097
Number of pages7
JournalNature Structural Biology
Volume5
Issue number12
DOIs
StatePublished - Dec 1998

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