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Publication Abstract from PubMed

The promising drug target N-myristoyltransferase (NMT) catalyses an essential protein modification thought to occur exclusively at N-terminal glycines (Gly). Here, we present high-resolution human NMT1 structures co-crystallised with reactive cognate lipid and peptide substrates, revealing high-resolution snapshots of the entire catalytic mechanism from the initial to final reaction states. Structural comparisons, together with biochemical analysis, provide unforeseen details about how NMT1 reaches a catalytically competent conformation in which the reactive groups are brought into close proximity to enable catalysis. We demonstrate that this mechanism further supports efficient and unprecedented myristoylation of an N-terminal lysine side chain, providing evidence that NMT acts both as N-terminal-lysine and glycine myristoyltransferase.

High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation.,Dian C, Perez-Dorado I, Riviere F, Asensio T, Legrand P, Ritzefeld M, Shen M, Cota E, Meinnel T, Tate EW, Giglione C Nat Commun. 2020 Feb 28;11(1):1132. doi: 10.1038/s41467-020-14847-3. PMID:32111831^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.