Identification of a Nonconserved Amino Acid Residue in Multidrug Resistance Protein 1 Important for Determining Substrate Specificity

@article{Zhang2001IdentificationOA,
  title={Identification of a Nonconserved Amino Acid Residue in Multidrug Resistance Protein 1 Important for Determining Substrate Specificity},
  author={D W Zhang and Susan P. C. Cole and Roger G. Deeley},
  journal={The Journal of Biological Chemistry},
  year={2001},
  volume={276},
  pages={34966 - 34974}
}
Murine multidrug resistance protein 1 (mrp1), differs from its human ortholog (MRP1) in that it fails to confer anthracycline resistance and transports the MRP1 substrate, 17β-estradiol 17-(β-d-glucuronide) (E217βG), very poorly. By mutating variant residues in mrp1 to those present in MRP1, we identified Glu1089of MRP1 as being critical for anthracycline resistance. However, Glu1089 mutations had no effect on E217βG transport. We have now identified a nonconserved amino acid within the highly… Expand
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An acidic amino acid residue at position 1089 in predicted TM14 of MRP1 is critical for the ability of the protein to confer drug resistance particularly to the anthracyclines, but is not essential for its ability to transport conjugated organic anions such as LTC4 and E217βG. Expand
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