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Transport of leukotriene C4 by a cysteine-less multidrug resistance protein 1 (MRP1).

ABSTRACT: Overexpression of multidrug resistance protein 1 (MRP1), an ATP-binding cassette protein, causes multidrug resistance. We developed a functional cysteine-less version of MRP1 that provides a framework for detailed biochemical and biophysical studies. The 18 Cys residues of a truncated MRP1 (tMRP1; lacking the first multispanning transmembrane domain) were replaced with Ala to generate Cys-less tMRP1 (CL tMRP1). CL tMRP1 expressed in Saccharomyces cerevisiae membranes displayed high-affinity ATP-dependent transport of the MRP1 substrate leukotriene C4. Compared with full-length MRP1, the K m for leukotriene C4 transport by CL tMRP1 was increased approximately 3-fold, while V max was not affected. Thus a functional CL tMRP1 can be expressed using a low-cost and rapid-generation yeast expression system. This Cys-less protein can be used for biochemical, spectroscopic and structural studies to elucidate the mechanism of drug transport by MRP1.

SUBMITTER: Lee SH

PROVIDER: S-EPMC1223133 | biostudies-literature | 2003 Feb

REPOSITORIES: biostudies-literature

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Transport of leukotriene C4 by a cysteine-less multidrug resistance protein 1 (MRP1).

Lee Sung H SH Altenberg Guillermo A GA

The Biochemical journal 20030201 Pt 1

Overexpression of multidrug resistance protein 1 (MRP1), an ATP-binding cassette protein, causes multidrug resistance. We developed a functional cysteine-less version of MRP1 that provides a framework for detailed biochemical and biophysical studies. The 18 Cys residues of a truncated MRP1 (tMRP1; lacking the first multispanning transmembrane domain) were replaced with Ala to generate Cys-less tMRP1 (CL tMRP1). CL tMRP1 expressed in Saccharomyces cerevisiae membranes displayed high-affinity ATP- ...[more]

PMID: 12398766

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Multidrug resistance-associated protein-1 (MRP1) genetic variants, MRP1 protein levels and severity of COPD.

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| S-EPMC2882908 | biostudies-literature

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Project description: Not available

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Chalcogenopyrylium dyes as differential modulators of organic anion transport by multidrug resistance protein 1 (MRP1), MRP2, and MRP4.

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| S-EPMC5589182 | biostudies-literature

Inhibition of multidrug resistance protein 1 (MRP1) improves chemotherapy drug response in primary and recurrent glioblastoma multiforme.

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