Analysis of Human Multidrug Resistance Protein 1 (ABCC1) by Matrix-Assisted Laser Desorption Ionization/Time of Flight Mass Spectrometry: Toward Identification of Leukotriene C4 Binding Sites

@article{Wu2005AnalysisOH,
  title={Analysis of Human Multidrug Resistance Protein 1 (ABCC1) by Matrix-Assisted Laser Desorption Ionization/Time of Flight Mass Spectrometry: Toward Identification of Leukotriene C4 Binding Sites},
  author={Peng Wu and Curtis J. Oleschuk and Qingcheng Mao and Bernd O. Keller and Roger G. Deeley and Susan P. C. Cole},
  journal={Molecular Pharmacology},
  year={2005},
  volume={68},
  pages={1455 - 1465}
}
Multidrug resistance in tumor cells may be caused by reduced drug accumulation resulting from expression of one or more proteins belonging to the ATP-binding cassette (ABC) transporter superfamily. In addition to their drug efflux properties, certain ABC proteins such as multidrug resistance protein 1 (MRP1) (ABCC1) mediate the ATP-dependent transport of a broad array of organic anions. The intrinsically photoreactive glutathione-conjugated cysteinyl leukotriene C4 (LTC4) is a high-affinity… 
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Effect of Multiple Cysteine Substitutions on the Functionality of Human Multidrug Resistance Protein 1 Expressed in Human Embryonic Kidney 293 Cells: Identification of Residues Essential for Function
TLDR
An almost cysless form of ΔMRP1 is produced that traffics to the plasma membrane and transports leukotriene C4, 17β-estradiol 17-β-d-glucuronide, and estrone-3-sulfate with kinetic characteristics similar to those of the wild-type protein.
Substrate recognition and transport by multidrug resistance protein 1 (ABCC1)
The predicted transmembrane fragment 17 of the human multidrug resistance protein 1 (MRP1) behaves as an interfacial helix in membrane mimics.
Biochemistry and Pharmacology of Human ABCC1/MRP1 and Its Role in Detoxification and in Multidrug Resistance of Cancer Chemotherapy
Structure‐guided probing of the leukotriene C4 binding site in human multidrug resistance protein 1 (MRP1; ABCC1)
TLDR
It is shown that single Ala and Leu substitutions of H‐pocket hMRP1‐Met1093 have no effect on LTC4 binding or transport, and it is demonstrated that these steroid conjugates have binding sites distinct from each other and from L TC4.
Structure of a human multidrug transporter in an inward-facing conformation.
Molecular analysis of the massive GSH transport mechanism mediated by the human Multidrug Resistant Protein 1/ABCC1
TLDR
The MRP1/MRP2 chimeras were generated and the sole restoration of the original G1228 (D1236 in MRP2) close to the extracellular loop between the two helices fully rescued the CS (massive GSH efflux and cell death) but not the MDR phenotype.
Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)
TLDR
An overview of the considerable amount of knowledge which has accumulated since the discovery of MRP1 is given, with special emphasis on the structural features essential for function, the recent understanding of the transport mechanism, and the numerous assignments of this transporter.
Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins.
TLDR
What is known of the structure of the MRPs and the mechanisms by which they recognize and transport their diverse substrates are described and evidence that they may be involved in the clinical drug resistance of various forms of cancer is summarized.
Mammalian multidrug-resistance proteins (MRPs).
TLDR
Important differences in the tissue distribution of the MRPs and their membrane localization in polarized cells also exist, which are responsible for the unique pharmacological and physiological functions of each of the nine ABCC transporters known as the MRP.
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TLDR
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