Fig. 4
From: Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus
Structure of Hsp90 nucleotide-binding domain (NBD) in complex with CMLD013075. a Ribbon representation of a 2.6 Å resolution crystal structure of CMLD013075 (blue) bound to C. albicans Hsp90 NBD. Radicicol from a separate C. albicans co-crystal (magenta) is overlaid. The ligands are represented as sticks and color-coded according to their heteroatom composition. b Detailed view of the binding mode of radicicol (top) and CMLD013075 (bottom) to C. albicans Hsp90. A surface representation is provided and color-coded by electrostatic potential (−10 to 10kT/e blue to red color ramp). c Binding affinities for CMLD013075 were determined by equilibrium competition FP assay using purified human Hsp90, fungal Hsp90, and human Grp94 NBDs and are indicated as Ki values. Assays were repeated in three independent experiments. The mean ± SEM is presented. Source data for the determination of binding affinities are provided as a source data file. d Polar contacts for the resorcinol-containing compound CMLD013075 in complex with C. albicans Hsp90 NBD. Protein residues engaged in H-bonds or cation–π interactions are labeled, and those interactions shown as dashed black lines. e H-bond networks of the residues selected for mutagenesis (bold residue names). Two fungal Hsp90 co-crystal structures are shown, radicicol (magenta), and CMLD013075 (cyan). For comparison, a human structure in complex with radicicol is also displayed (PDB id. 4EGK).
