SOLUBILIZATION AND CHARACTERIZATION OF THE OVEREXPRESSED PDR5 MULTIDRUG-RESISTANCE NUCLEOTIDE TRIPHOSPHATASE OF YEAST

A 160-kDa plasma membrane protein of the yeast Saccharomyces cerevisia e was overexpressed by mutating the PDR1 or the PDR3 transcription fac tor gene. The protein is the membrane-bound ATP binding cassette trans porter PDR5 (Balzi, E., Wang, M., Leterme, S., Van Dyck, L., and Goffe au, A. (1994) J. Biol. Chem. 269, 2206-2214). PDR5 was solubilized wit h n-dodecyl-beta-D-maltoside and separated from the PMA1 plasma membra ne H+-ATPase by glycerol gradient centrifugation. The PDR5 protein hyd rolyzes nucleoside diphosphates and triphosphates. This activity is se nsitive to low concentrations of vanadate, of oligomycin, and of a var iety of hydrophobic compounds. Many of these properties liken PDR5 to the purified mammalian P-glycoprotein responsible for multidrug resist ance.