7OWR
HsNMT1 in complex with both MyrCoA and peptide GGKSFSKPR
Summary for 7OWR
| Entry DOI | 10.2210/pdb7owr/pdb |
| Descriptor | Glycylpeptide N-tetradecanoyltransferase 1, GLY-GLY-LYS-SER-PHE-SER-LYS-PRO-ARG, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | n-myristoylation, nmt, myristoyltransferase type1, acyltransferase, gnat, gcn5-related n-acetyltransferases, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 96129.01 |
| Authors | Dian, C.,Giglione, C.,Meinnel, T. (deposition date: 2021-06-18, release date: 2022-12-21, Last modification date: 2024-01-31) |
| Primary citation | Riviere, F.,Dian, C.,Dutheil, R.F.,Monassa, P.,Giglione, C.,Meinnel, T. Structural and Large-scale Analysis Unveil the Intertwined Paths Promoting NMT-catalyzed Lysine and Glycine Myristoylation. J.Mol.Biol., 434:167843-167843, 2022 Cited by PubMed Abstract: N-myristoyltransferases (NMTs) catalyze protein myristoylation, a lipid modification crucial for cell survival and a range of pathophysiological processes. Originally thought to modify only N-terminal glycine α-amino groups (G-myristoylation), NMTs were recently shown to also modify lysine ε-amino groups (K-myristoylation). However, the clues ruling NMT-dependent K-myristoylation and the full range of targets are currently unknown. Here we combine mass spectrometry, kinetic studies, in silico analysis, and crystallography to identify the specific features driving each modification. We show that direct interactions between the substrate's reactive amino group and the NMT catalytic base promote K-myristoylation but with poor efficiency compared to G-myristoylation, which instead uses a water-mediated interaction. We provide evidence of depletion of proteins with NMT-dependent K-myristoylation motifs in humans, suggesting evolutionary pressure to prevent this modification in favor of G-myristoylation. In turn, we reveal that K-myristoylation may only result from post-translational events. Our studies finally unravel the respective paths towards K-myristoylation or G-myristoylation, which rely on a very subtle tradeoff embracing the chemical landscape around the reactive group. PubMed: 36181773DOI: 10.1016/j.jmb.2022.167843 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.39 Å) |
Structure validation
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