Fig. 5: Mechanistic model of gyrase inhibition by albicidin.

a, Initial state: an apo-gyrase complex. b, G-segment DNA fragment is engaged and bound. c, T-segment DNA fragment is captured by the ATPase domains of GyrB and the DNA is cleaved. d, The T-segment is transported through the enzyme, stimulated by the ATP binding (blue hexagons), causing dimerization of the ATPase domains. e, The T-segment is transported to the bottom chamber of the enzyme and the DNA has to be religated to release the T-segment. Albicidin intercalates in DNA in outer-rotated conformation (XT state). f, Albicidin rotates and occupies the binding pocket between two GyrA monomers. g, Albicidin effectively jams the enzyme movement, blocking the escape into any productive state. Inset: an enlarged scheme of albicidin–DNA–gyrase interaction in the locked state. h, Scheme of albicidin molecule, consisting of two rigid fragments (N- and C-terminal), connected by a flexible hinge residue, While in our structure the compound has L shape (‘L’), it adopts a more open wide-angle V shape (‘V’) in complex with the AlbA resistance protein (PDB: 6ET8)²⁷.