Multidrug transporter

FIGURE 10.18 A model for the structure of the a-factor transport protein in the yeast plasma membrane. Gene duplication has yielded a protein with two identical halves, each half containing six transmembrane helical segments and an ATP-binding site. Like the yeast a-factor transporter, the multidrug transporter is postulated to have 12 transmembrane helices and 2 ATP-binding sites. 

II Gottesman, I Pastan. Biochemistry of multidrug resistance mediated by the multidrug transporter. Ann Rev Biochem 62 385-427, 1993. 

S. J., Goldenberg, S., Wiliams, C., Pasatan, I., Gottesman, M. M., Handler, J., Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epifhelia, J. Biol. Chem. 1989, 264, 14880-14884. 

The recent crystallization of the small water-soluble transcriptional regulator of Bacillus subtilis multidrug transporter Bmr, BmrR, which binds hydrophobic cations from the cytosol [64, 65] provides a good example for an interaction determined primarily by van der Waals interactions. Interestingly, the same drugs, which bind to the water-soluble BmrR are also substrates for the transmembrane multidrug transporter Bmr. As will be discussed below, the latter interactions could well be of different nature. 

Sarkadi, B., Muller, M., Hollo, Z., The multidrug transporters - proteins of an ancient immune system, Immunol. Lett. 1996, 54, 215-219. 

H., Gottesman, M. M., Pastan, I., Willingham, M. C., Immunohisto-chemical localization in normal tissues of different epitopes in the multidrug transport protein PI70 evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein, J. Histochem. Cytochem. 1989, 37, 159-164. 

Romsicki, Y., Sharom, F. J., Phospholipid flippase activity of the reconstituted P-glycoprotein multidrug transporter, Biochemistry 2001, 40, 6937-6947. 

Hollo, Z., Homolya, L., Davis, C. W., Sarkadi, B., Calcein accumulation as a fluorometric functional assay of the multidrug transporter, Biochim. 

Epel D (1998) Use of multidrug transporters as first lines of defense against toxins in aquatic organisms. Comp Biochem Physiol 120 23-28... 

Mizuarai, S., Aozasa, N., and Kotani, H. (2004) Single nucleotide polymorphisms result in impaired membrane localization and reduced atpase activity in multidrug transporter ABCG2. Int. J. Cancer 109, 238-246. 

Allen, J. D., Jackson, S. C., and Schinkel, A. H. (2002) A mutation hot spot in the BCRPl (ABCG2) multidrug transporter in mouse cell fines selected for doxorubicin resistance. Cancer Res. 62, 2294-2299. 

Many non-target organisms (which possess human- and animal-alike metabolic pathways, similar receptors or biomolecules) are inadvertently exposed to these substances [40, 58]. Since several APIs are known to interact with Cytochrome P-450, there is a potential risk of disruption in the homeostasis of non-target organisms. Moreover, pharmaceuticals that interact with the Glycoprotein-P (P-gp), a multidrug transporter that actively transports xenobiotics out of the cell, increase their sensitivity to environmental pollutants [17]. 

Luckenbach T, Epel D (2005) Nitromusk and polycyclic musk compounds as long-term inhibitors of cellular xenobiotic defense systems mediated by multidrug transporters. Environ Health Perspect 113 17-24... 

Johnstone RW, Ruefli AA, Smyth MJ. Multiple physiological functions for multidrug transporter P-glycoprotein. Trends Biochetn Sci 2000 25 1-6. 

Aftab DT, Yang JM, HaitWN (1994) Functional role of phosphorylation of the multidrug transporter (P-glycoprotein) by protein kinase C in multidrug-resistant MCF-7 cells. Oncol Res 6 59-70... 

Egner R, Kuchler K (1996) The yeast multidrug transporter Pdr5 of the plasma membrane is ubiquitinated prior to endoq osis and degradation in the vacuole. FEES Lett 378 177-181... 

Blackmore CG, McNaughton PA, and van Veen HW. Multidrug transporters in prokaryotic and eukaryotic cells physiological functions and transport mechanisms. Mol Membr Biol 2001 18 97-103. 

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