Abstract
The human multidrug resistance protein (MDR1) (P-glycoprotein), a member of the ATP-binding cassette (ABC) family, causes multidrug resistance by an active transport mechanism, which keeps the intracellular level of hydrophobic compounds below a cell-killing threshold. Human MDR1 variants with mutations affecting a conserved glycine residue within the ABC signature of either or both ABC units (G534D, G534V, G1179D and G534D/G1179D) were expressed and characterized in Spodoptera frugiperda (Sf9) cell membranes. These mutations caused a loss of measurable ATPase activity but still allowed ATP binding and the formation of a transition-state intermediate (nucleotide trapping). In contrast with the wild-type protein, in which substrate drugs accelerate nucleotide trapping, in the ABC signature mutants nucleotide trapping was inhibited by MDR1-substrate drugs, suggesting a miscommunication between the drug-binding site(s) and the catalytic domains. Equivalent mutations of the two catalytic sites resulted in a similar effect, indicating the functional equivalence of the two sites. On the basis of these results and recent structural information on an ABC-ABC dimer [Hopfner, Karcher, Shin, Craig, Arthur, Carney and Tainer (2000) Cell 10...Continue Reading
References
Jan 1, 1992·Annual Review of Cell Biology·C F Higgins
Sep 18, 1992·Science·M P Anderson, M J Welsh
Sep 1, 1991·Journal of Cellular Physiology·E GeorgesV Ling
Nov 10, 1995·The Journal of Biological Chemistry·I L UrbatschA E Senior
Aug 18, 1995·The Journal of Biological Chemistry·I L UrbatschA E Senior
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Dec 27, 1995·FEBS Letters·A E SeniorI L Urbatsch
Apr 18, 1997·The Journal of Biological Chemistry·M F RosenbergC F Higgins
May 1, 1997·Archives of Biochemistry and Biophysics·B SankaranA E Senior
Jun 3, 1997·Biochemistry·B SankaranA E Senior
May 30, 1998·The Journal of Biological Chemistry·K SzabóB Sarkadi
Sep 29, 1998·Biochemical Pharmacology·R L ShepardA H Dantzig
Jan 1, 1999·Nature·L W HungS H Kim
Aug 24, 1999·The Journal of Biological Chemistry·T W Loo, D M Clarke
Nov 24, 1999·European Journal of Biochemistry·G SchmeesE Schneider
Dec 3, 1999·Biochimica Et Biophysica Acta·I KleinA Váradi
Jul 13, 2000·Cell·K P HopfnerJ A Tainer
Oct 12, 2000·Biochemical and Biophysical Research Communications·G SzakácsA Váradi
Citations
Dec 26, 2006·Pflügers Archiv : European journal of physiology·Eva Bakos, László Homolya
Mar 26, 2003·European Journal of Biochemistry·Georgina BerridgeIan D Kerr
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cedric OrelleAmy L Davidson
Jul 3, 2009·The Journal of Biological Chemistry·Sonia PaytubiChristopher G Proud
Aug 10, 2002·The EMBO Journal·Michinori MatsuoFrances M Ashcroft
Jun 5, 2002·Annual Review of Biochemistry·P Borst, R Oude Elferink
May 3, 2006·Cancer Research·Joseph A LudwigMichael M Gottesman
May 17, 2011·BMC Biochemistry·Ahmad FirozShandar Ahmad
Sep 22, 2011·PloS One·Olivier Le SauxAndrás Váradi
Jul 5, 2001·Biochemical and Biophysical Research Communications·C OzvegyB Sarkadi
Jul 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Erin E Fetsch, Amy L Davidson
Feb 9, 2012·Journal of Amino Acids·Rajendra PrasadManpreet Kaur Rawal
Dec 20, 2013·The Journal of Investigative Dermatology·Viola PomoziAndrás Váradi
Aug 28, 2010·Protein Science : a Publication of the Protein Society·Libusha KellyAndrej Sali
Jul 9, 2004·Biochemical and Biophysical Research Communications·Cheol-Hee ChoiSang-Hyun Kim
May 1, 2007·Environmental Toxicology and Pharmacology·Joon-Ho KimCheol-Hee Choi
Dec 15, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Suresh V AmbudkarZuben E Sauna
Aug 10, 2005·Mutation Research·Lynnette R Ferguson, Silvio De Flora
Jan 27, 2005·Biochimica Et Biophysica Acta·Csilla Ozvegy-LaczkaAndrás Váradi
Sep 12, 2015·BioMed Research International·Eva Y G De VilderOlivier M Vanakker
Aug 14, 2012·Biochimica Et Biophysica Acta·Marc LiesaOrian S Shirihai
Jan 30, 2015·The Biochemical Journal·Katalin KissGergely Szakacs
May 24, 2008·Biochimica Et Biophysica Acta·Versha RaiRajendra Prasad
Nov 24, 2007·Biochimica Et Biophysica Acta·J LawsonI D Kerr
Jun 16, 2010·Biochimica Et Biophysica Acta·Antresh KumarRajendra Prasad
Oct 11, 2002·The Journal of Biological Chemistry·Csilla OzvegyBalázs Sarkadi
Sep 25, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Agnes KarasikFlóra Szeri
Aug 24, 2004·The Journal of Biological Chemistry·Min ChenRobert Tampé
Nov 8, 2002·The Journal of Biological Chemistry·Tip W LooDavid M Clarke