Fig. 3.

Inhibitors (I) can stabilize the cleaved state through binding at different positions. (A) View of the un-cleaved binary complex equivalent to Fig. 2c. (B) Closer view of the binary complex (6FQV) showing the proximity of the two Asp83 residues at the WHDs interface. (C) Global view of compound binding sites on the S. aureus gyrase^CORE illustrated by moxifloxacin (in sites 1 and 1′), GSK299423 (in site 2) and thiophene 2 (in sites 3 and 3″). The structure represented is a composite between a thiophene 2 and GSK945237 bound structure (PDB code: 5NPP) and a moxifloxacin-bound structure (PDB code: 5CDQ). (D) Closer view of the moxifloxacin structure (5CDQ) showing moxifloxacin (I1 and I201), Mn²⁺ (yellow sphere) and the separation of the Asp83 residues. (E) Alternative view of the composite representation shown in panel C. (F) Closer view of the NBTIs/thiophene structure (5NPP) showing GSK945237 (2), and thiophene 2 (3 and 3′), Mn²⁺ (yellow sphere) and the separation of the two Asp83 residues.