Interaction of prenylcysteine methyl esters with the multidrug resistance transporter.

Journal Article (Journal Article)

The multidrug resistance transporter is an integral membrane protein, termed P-glycoprotein, which can function as an ATP-dependent drug efflux pump to reduce intracellular drug accumulation in treated cells. The physiologic function of this protein in normal cells, however, is not completely understood. We report here that prenylcysteine methyl esters, which represent the C-terminal structures of prenylated proteins, both stimulate the transporter's intrinsic ATPase activity and compete for drug binding. The structural elements of prenylcysteine methyl esters involved in their interaction with P-glycoprotein include the isoprenoid moiety, the carboxyl methyl group, and the free amino group. These findings indicate that these molecules are potential physiologic ligands of the transporter. Furthermore, as the structures of the active prenylcysteines are distinct from the known substrates of P-glycoprotein, this information may facilitate design of novel inhibitors of the transporter.

Full Text

Duke Authors

Cited Authors

  • Zhang, L; Sachs, CW; Fine, RL; Casey, PJ

Published Date

  • June 10, 1994

Published In

Volume / Issue

  • 269 / 23

Start / End Page

  • 15973 - 15976

PubMed ID

  • 7911465

International Standard Serial Number (ISSN)

  • 0021-9258


  • eng

Conference Location

  • United States