“…S1368A exhibited profound, broad multidrug hypersensitivity, and yet its ATPase activity was indistinguishable from WT, as was the allosteric inhibition (trans inhibition) of this enzyme by clo. Previously reported mutations in Pdr5 with broad hypersensitivity, such as K911A (Walker A), E1036Q, and G312A, exhibited either a strong reduction in steady-state ATPase activity (13,20) or a loss of communication between the transmembrane domains and NBDs causing a large reduction in allosteric inhibition (14,17). This includes the S1360F mutant, which is in the same TMH as S1368A (21,24).…”