PMC

Inhibition and binding of compound 12. (a) Dose-response curve for CTX-M. The error for any point is 2% activity or less. (b) CTX-M complex structure (stereoview). Potential hydrogen bonds are represented by black dash lines. A mediating water molecule is shown as a red sphere.

Crystal structures of fragment inhibitors and optimized derivatives against CTX-M. Five compounds have molecular weight below 250 Da, with two additional ones below 300. The surface of the protein active site is colored white (carbon), red (oxygen) and blue (nitrogen). The crystal pose of the ligand is colored yellow. The docking prediction is shown in cyan. The 2F_o − F_c electron density of the ligands is shown in white at 1σ. For compound 4, the active site is shared by the inhibitor and a phosphate molecule, both modeled at half occupancy. For compound 11, there is a partial-occupancy phosphate in the active site that is not shown here. Waters with half occupancy are also modeled in the structures of compounds 3 and 6.