Fig. 5: Structural analysis of narbonolide (7)-bound and narbomycin (5)-bound PikCH238pAcF.
a, b Molecular modeling of 7 within the substrate binding pocket of PikCH238pAcF: comparisons of contacting amino acid side chains around the substrate binding site within 4.5 Å between 7-bound PikCH238pAcF and substrate-free PikCWT (a) and 5-bound PikCD50N (b). The side chains are shown as sticks in grey (PikCH238pAcF), forest (substrate-free PikCWT), and salmon (5-bound PikCD50N). The heme groups are colored consistent with the corresponding substrates. The hydrogen bonds are shown as dashed black line. c Schematic diagram of the positions of 5 in superimposed PikCH238pAcF and PikCD50N. The salt bridges formed between the acidic amino acid residues and the C3’ dimethylamino group of the desosamine moiety in 5 are shown as yellow dashed lines. d, e The substrate binding pockets formed by the amino acid side chains within 4.5 Å from 5 in the 5-bound PikCH238pAcF (d) and 5-bound PikCD50N (e). The newly involved residues are labeled in red and the missing residues in blue. f Detailed view of the hydrogen bond network formed by pAcF238, E94 and 5 through three water molecules in 5-bound PikCH238pAcF. The water molecules are shown as red spheres, and the weighted 2Fo–Fc electron density map is contoured at the level of 1.0 σ (blue mesh). The hydrogen bonds in angstrom are shown as dashed black lines.
