Fig. 7: Molecular interactions of LEI-800 explain the mutation data and SAR. | Nature Chemistry

Fig. 7: Molecular interactions of LEI-800 explain the mutation data and SAR.

From: Discovery of isoquinoline sulfonamides as allosteric gyrase inhibitors with activity against fluoroquinolone-resistant bacteria

Fig. 7

a, Molecular interactions between GyrA and LEI-800. LEI-800 is shown as stick representation. The main GyrA residues important for LEI-800 binding are labelled. Key hydrogen bonds (between side-chain and main-chain oxygens of Ser97 and N3 nitrogen of central pyrrolidine ring of LEI-800; main chain nitrogen of Ser172, side-chain nitrogen of Lys42 and sulfonic acid of LEI-800 are shown in gold and distances in Angstrom are indicated. b, A comparison of LEI-800 (current study), CIP (PDB: 2XCT) and SD8 (PDB: 4CKL) binding sites on the GyrA DNA-binding surface. LEI-800 is shown as golden, SD8 as pink and CIP as grey stick representations. A quinoline ring of LEI-800 shares the binding pocket with the aminocoumarin moiety of SD8, but unlike SD8, LEI-800 does not interfere with DNA binding. c, A 2D diagram of the LEI-800 binding site generated by LigPlot44. Key hydrogen bonds to Ser97 and Ser172 are shown in black and distances in Å are indicated. Spiked red arcs show non-bonded interactions and green arcs hydrophobic interactions with residues within 3.9 Å distance.

Back to article page