Fig. 9.

Radicicol resistance by modification of the ATP-binding site of Hsp90. A single mutation, L34I results in the opening of a pocket that alters the water structure of the active site. Three additional water molecules enter and repel the chlorine (Cl) of radicicol thus decreasing its affinity for Hsp90. Water molecules are shown as pale yellow (L34I) and cyan (wild type) spheres. Radicicol bound to the mutant protein is shown in yellow while that bound to wild type Hsp90 is in cyan. Amino acid residues of L34I are in yellow and residues of the wild type protein are in cyan. Mutations are shown as L34I and V35I in red text. Dotted red (L34I) and blue lines (wild type) represent hydrogen bonds.