Nucleotide triphosphatase activity of the N-terminal nucleotide-binding domains of the multidrug resistance proteins P-glycoprotein and MRP1

Denise M. Wilkes, Changsen Wang, Patricia C. Aristimuo, Ariel F. Castro, Guillermo A. Altenberg

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The multidrug resistance proteins P-glycoprotein (Pgp) and MRP1 are drug-efflux pumps. In this study, we compared the nucleotide triphosphatase activities of the isolated N-terminal nucleotide binding domains (NBD1) of Pgp and MRP1, and explored the potential role of the phosphorylation target domain of Pgp on the regulation of Pgp NBD1 ATPase activity. We found that: (1) the NBD1s of Pgp and MRP1 have ATPase and GTPase activities, (2) the Kms of Pgp NBD1 for ATP and GTP hydrolysis are identical, while the Km of MRP1 NBD1 for ATP is lower than that for GTP, and (3) phosphorylation of MLD by PKA or PKC produces a marginal increase of Vmax for ATP hydrolysis, without affecting the affinity for ATP. These results show efficient GTP hydrolysis by the NBD1s of Pgp and MRP1, and a minor role of phosphorylation in the control of Pgp NBD1 ATPase activity.

Original languageEnglish (US)
Pages (from-to)388-394
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume296
Issue number2
DOIs
StatePublished - Oct 14 2002

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Keywords

  • ABC proteins
  • CFTR
  • Expression
  • Maltose-binding protein
  • Multidrug resistance
  • Nucleotide-binding fold
  • Phosphorylation
  • Purification
  • R domain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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