6SJZ

HsNMT1 in complex with both MyrCoA and Acetylated-GNCFSKPR substrates

Summary for 6SJZ

• Entry DOI: 10.2210/pdb6sjz/pdb
• Descriptor: Glycylpeptide N-tetradecanoyltransferase 1, Apoptosis-inducing factor 3, TETRADECANOYL-COA, ... (6 entities in total)
• Functional Keywords: nmt, myristoyltransferase type1, acyltransferase, gnat, gcn5-related n-acetyltransferases, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 97198.07

Authors

Dian, C.,Riviere, F.B.,Asensio, T.,Giglione, C.,Meinnel, T. (deposition date: 2019-08-14, release date: 2020-03-18, Last modification date: 2024-10-16)

Primary citation

Dian, C.,Perez-Dorado, I.,Riviere, F.,Asensio, T.,Legrand, P.,Ritzefeld, M.,Shen, M.,Cota, E.,Meinnel, T.,Tate, E.W.,Giglione, C.
High-resolution snapshots of human N-myristoyltransferase in action illuminate a mechanism promoting N-terminal Lys and Gly myristoylation.
Nat Commun, 11:1132-1132, 2020

PubMed Abstract: 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.

PubMed: 32111831
DOI: 10.1038/s41467-020-14847-3

Experimental method

X-RAY DIFFRACTION (1.995 Å)