7own

HsNMT1 in complex with both MyrCoA and peptide AKSFSKPR

spinqualitylabelsall models 7own, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7own is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: GOL, MYA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NMT1_HUMAN Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins. Publication Abstract from PubMed 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 alpha-amino groups (G-myristoylation), NMTs were recently shown to also modify lysine epsilon-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. Structural and Large-scale Analysis Unveil the Intertwined Paths Promoting NMT-catalyzed Lysine and Glycine Myristoylation.,Riviere F, Dian C, Dutheil RF, Monassa P, Giglione C, Meinnel T J Mol Biol. 2022 Nov 30;434(22):167843. doi: 10.1016/j.jmb.2022.167843. Epub 2022 , Sep 29. PMID:36181773 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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