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Interaction of prenylcysteine methyl esters with the multidrug resistance transporter.

Publication ,  Journal Article
Zhang, L; Sachs, CW; Fine, RL; Casey, PJ
Published in: J Biol Chem
June 10, 1994

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.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

June 10, 1994

Volume

269

Issue

23

Start / End Page

15973 / 15976

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Terpenes
  • Substrate Specificity
  • Recombinant Proteins
  • Protein Prenylation
  • Moths
  • Membrane Glycoproteins
  • Ligands
  • Humans
  • Esters
 

Citation

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Zhang, L., Sachs, C. W., Fine, R. L., & Casey, P. J. (1994). Interaction of prenylcysteine methyl esters with the multidrug resistance transporter. J Biol Chem, 269(23), 15973–15976.
Zhang, L., C. W. Sachs, R. L. Fine, and P. J. Casey. “Interaction of prenylcysteine methyl esters with the multidrug resistance transporter.J Biol Chem 269, no. 23 (June 10, 1994): 15973–76.
Zhang L, Sachs CW, Fine RL, Casey PJ. Interaction of prenylcysteine methyl esters with the multidrug resistance transporter. J Biol Chem. 1994 Jun 10;269(23):15973–6.
Zhang, L., et al. “Interaction of prenylcysteine methyl esters with the multidrug resistance transporter.J Biol Chem, vol. 269, no. 23, June 1994, pp. 15973–76.
Zhang L, Sachs CW, Fine RL, Casey PJ. Interaction of prenylcysteine methyl esters with the multidrug resistance transporter. J Biol Chem. 1994 Jun 10;269(23):15973–15976.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

June 10, 1994

Volume

269

Issue

23

Start / End Page

15973 / 15976

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Terpenes
  • Substrate Specificity
  • Recombinant Proteins
  • Protein Prenylation
  • Moths
  • Membrane Glycoproteins
  • Ligands
  • Humans
  • Esters