6EHJ

Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and peptide bound

Summary for 6EHJ

• Entry DOI: 10.2210/pdb6ehj/pdb
• Related: 4C2Y 4C2Z
• Descriptor: Glycylpeptide N-tetradecanoyltransferase 1, COENZYME A, GLYCEROL, ... (11 entities in total)
• Functional Keywords: myristoylation, complex, substrate peptide, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 96192.94

Authors

Perez-Dorado, I.,Ritzefeld, M.,Tate, E.W. (deposition date: 2017-09-13, release date: 2019-03-27, Last modification date: 2024-01-17)

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 (2.1 Å)