S-Decyl-glutathione nonspecifically stimulates the ATPase activity of the nucleotide-binding domains of the human multidrug resistance-associated protein, MRP1 (ABCC1)

RH Cool*, MK Veenstra, W van Klompenburg, RIR Heyne, M Muller, EGE de Vries, HW van Veen, WN Konings

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

8 Citaten (Scopus)

Samenvatting

The human multidrug resistance-associated protein(MRP1) is an ATP-dependent efflux pump that transports anionic conjugates, and hydrophobic compounds in a glutathione dependent manner. Similar to the other, well-characterized multidrug transporter P-gp, MRP1 comprises two nucleotide-binding domains (NBDs) in addition to transmembrane domains. However, whereas the NBDs of P-gp have been shown to be functionally equivalent, those of MRP1 differ significantly. The isolated NBDs of MRP1 have been characterized in Escherichia coli as fusions with either the glutathione-S -transferase (GST) or the maltose-binding domain (MBP). The nonfused NBD1 was obtained by cleavage of the fusion protein with thrombin. The GST-fused forms of NBD1 and NBD2 hydrolyzed ATP with an apparent K (m) of 340 mum and a V (max) of 6.0 nmol P-I .mg(-1) .min(-1) , and a K (m) of 910 mum ATP and a V (max) of 7.5 nmol P-I .mg(-1) .min(-1) , respectively. Remarkably, S -decyl-glutathione, a conjugate specifically transported by MRP1 and MRP2, was able to stimulate the ATPase activities of the isolated NBDs more than 2-fold in a concentration-dependent manner. However,the stimulation of the ATPase activity was found to coincide with the formation of micelles by S -decyl-glutathione. Equivalent stimulation of ATPase activity could be obtained by surfactants with similar critical micelle concentrations.

Originele taal-2English
Pagina's (van-tot)3470-3478
Aantal pagina's9
TijdschriftEuropean Journal of Biochemistry
Volume269
Nummer van het tijdschrift14
DOI's
StatusPublished - jul-2002

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