6fz5

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

spinqualitylabelsall models 6fz5, resolution 1.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fz5 is a 2 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 1.89Å Ligands: BXN, GOL, MG, 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 A model system of two related enzymes with conserved binding sites, namely N-myristoyltransferase from two different organisms, was studied to decipher the driving forces that lead to selective inhibition in such cases. Using a combination of computational and experimental tools, two different selectivity-determining features were identified. For some ligands, a change in side-chain flexibility appears to be responsible for selective inhibition. Remarkably, this was observed for residues orienting their side chains away from the ligands. For other ligands, selectivity is caused by interfering with a water molecule that binds more strongly to the off-target than to the target. On the basis of this finding, a virtual screen for selective compounds was conducted, resulting in three hit compounds with the desired selectivity profile. This study delivers a guideline on how to assess selectivity-determining features in proteins with conserved binding sites and to translate this knowledge into the design of selective inhibitors. How To Design Selective Ligands for Highly Conserved Binding Sites: A Case Study Using N-Myristoyltransferases as a Model System.,Kersten C, Fleischer E, Kehrein J, Borek C, Jaenicke E, Sotriffer C, Brenk R J Med Chem. 2019 Aug 19. doi: 10.1021/acs.jmedchem.9b00586. PMID:31423787 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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