Extended Data Fig. 9: Structures of the drug in the complex superimpose well.

a) Superposition of 25 structures (lines and cartoon representations) of four teixobactin bound to four Lipid II molecules (not shown). The average backbone RMSD is 2.3 +/− 0.6 Å (from the average structure). We calculated the structure of four teixobactin and four (4 x 4) Lipid II (quartet) instead of a 2 x 2 unit (dimer) to obtain a better description of the intermolecular interactions. In a dimer, half of the backbone hydrogen bonds cannot form, and the repetitive interactions between sidechains along the fibril axis are truncated. The description is improved in a quartet, in which intermolecular interactions are complete for the inner dimer, which is the reason why the inner teixobactin molecules are better defined than the outer ones. b) The network of hydrophilic residues on the water-exposed side creates opportunities for hydrogen bonding between the sidechains of D-Gln4. Moreover, MD simulations suggest that the hydroxyl-group of Ser7 favourably interacts with the Lipid II PPi group. c) Green lines show hydrogen bonds and favourable electrostatics between End10 and MurNAcC6OH. The unambiguous, short ssNMR contacts of End10Cζ with MurNAcC5 and MurNAcC6 are highlighted with thick continuous lines. Distances in the NMR structure: Ala9Cβ – MurNAcC1 = 4.0 Å. Ala9Cβ – MurNAcC3 = 6.4 Å. End10Cζ – MurNAcC6 = 4.1 Å. End10Cζ – MurNAcC5 = 5.2 Å. End10Cζ – MurNAcC4 = 5.1 Å. End10Cζ – MurNAcC3 = 6.4 Å. End10Cζ – MurNAcC1 = 6.6 Å. End10Cδ – MurNAcC5 = 5.7 Å. End10Cγ – MurNAcC5 = 5.9 Å. End10Cγ – MurNAcC3 = 7.0 Å. End10Cγ – MurNAcC1 = 6.6 Å. End10Cβ – MurNAcC1 = 5.6 Å. Phe1MeN – MurNAcC3 = 6.0 Å. Phe1MeN – MurNAcC5 = 7.2 Å. End10Nδ – MurNAcC6OH = 2.6 Å (hydrogen bond/electrostatic interaction). End10Nε – MurNAcC6OH = 2.2 Å (hydrogen bond/electrostatic interaction). End10Nζ – MurNAcC6OH = 3.2 Å (hydrogen bond/electrostatic interaction).