Functional Studies on the MRP1 Multidrug Transporter

Characterization of ABC-signature Mutant Variants

Zsófia Szentpétery, B. Sarkadi, E. Bakos, A. Váradi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: MRP1 is a key multidrug resistance ATP-binding Cassette (ABC) transporter in tumor cells. A functionally important signature motif is conserved within all ABC domains. Our current studies aimed to elucidate the role of these motifs in the cooperation of MRP1 ABC domains. Materials and Methods: We designed human MRP1 mutants based on a bacterial ABC structure. Conserved leucines (Leu) were replaced by arginines (Arg), while glycines (Gly) were substituted for aspartic acids (Asp). The activity of these mutants was assayed by measuring ATPase activity and vesicular transport. A TP-binding and transition-state formation were studied by a photoreactive ATP analog. Results: The Leu to Arg mutants retained both ATPase and transport activity, while the Gly to Asp mutants were inactive in all functional assays, while showing normal A TP-binding. Conclusion: Our results reinforce the notion that a single mutation in one of the ABC-signature regions affects the function of the whole protein. The relative role of the conservative leucines and glycines in MRP1 indicates a similar three-dimensional structure within the catalytic center of various ABC proteins.

Original languageEnglish
Pages (from-to)449-455
Number of pages7
JournalAnticancer Research
Volume24
Issue number2 A
Publication statusPublished - Mar 2004

Fingerprint

ATP-Binding Cassette Transporters
Adenosine Triphosphate
Leucine
Glycine
Viperidae
Adenosine Triphosphatases
Arginine
Multiple Drug Resistance
Aspartic Acid
Carrier Proteins
Mutation
Neoplasms
Proteins

Keywords

  • ABC-ABC structure
  • ABC-signature
  • ATP-binding Cassette
  • MRP1
  • Multidrug resistance
  • Nucleotide trapping

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Functional Studies on the MRP1 Multidrug Transporter : Characterization of ABC-signature Mutant Variants. / Szentpétery, Zsófia; Sarkadi, B.; Bakos, E.; Váradi, A.

In: Anticancer Research, Vol. 24, No. 2 A, 03.2004, p. 449-455.

Research output: Contribution to journalArticle

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