Localization and effects of mutations on ATPase activities. (a) Mutated residues are shown as red spheres in the crystal structure of closed yeast Hsp90 (PDB 2CG9)18. Blue, N domain; green, M domain; orange, C domain; cyan, lid structure. (b) Influence of mutations on the ATPase activity of Hsp90. Coupled enzymatic ATPase assay (gray bars). Data are shown as mean ± s.d. (n = 3 technical replicates). Inset, kcat values of the Hsp90 variants in the presence of various concentrations of ATP: black, WT; yellow, A107N; blue, Δ8; green, T22I; purple, R346S; gray, R380A; red, E33A; cyan, D79N. (c) Stimulation of Hsp90 ATPase by the cochaperone Aha1, determined by a coupled enzymatic ATPase assay. Fold increases in ATPase activity in the presence of Aha1 are shown. Inset, kcat values of the Hsp90 mutants in the presence of various Aha1 concentrations: black, WT; yellow, A107N; blue, Δ8; green, T22I; purple, R346S; gray, R380A; red, E33A; cyan, D79N. (d) Viability of the Hsp90 variants deduced by a 5-fluoroorotic acid (5-FOA) shuffling assay. Shuffling experiments were carried out at least three times and represent technical replicates started from independent single yeast colonies. (e) Western blot analysis showing expression of Hsp90 in yeast cells after 5-FOA shuffling. PGK1, loading control.