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Is ATP binding responsible for initiating drug translocation by the multidrug transporter ABCG2?

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  • معلومة اضافية
    • المصدر:
      Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 101229646 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1742-464X (Print) Linking ISSN: 1742464X NLM ISO Abbreviation: FEBS J Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: Oxford, UK : Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies, c2005-
    • الموضوع:
      ATP-Binding Cassette Transporters/*physiology ; Adenosine Triphosphate/*metabolism ; Antineoplastic Agents/*metabolism ; Daunorubicin/*metabolism ; Neoplasm Proteins/*physiology; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Animals ; Antineoplastic Agents/pharmacokinetics ; Cell Line ; Daunorubicin/pharmacokinetics ; Moths ; Protein Binding ; Radioligand Assay ; Tritium
    • نبذة مختصرة :
      ABCG2 confers resistance to cancer cells by mediating the ATP-dependent outward efflux of chemotherapeutic compounds. Recent studies have indicated that the protein contains a number of interconnected drug binding sites. The present investigation examines the coupling of drug binding to ATP hydrolysis. Initial drug binding to the protein requires a high-affinity interaction with the drug binding site, followed by transition and reorientation to the low-affinity state to enable dissociation at the extracellular face. [3H]Daunomycin binding to the ABCG2 R482G isoform was examined in the nucleotide-bound and post-hydrolytic conformations. Binding of [3H]daunomycin was displaced by ATP analogues, indicating transition to a low-affinity conformation prior to hydrolysis. The low-affinity state was observed to be retained immediately post-hydrolysis. Therefore, the dissociation of phosphate and/or ADP is likely to be responsible for resetting of the transporter. The data indicate that, like ABCB1 and ABCC1, the 'power stroke' for translocation in ABCG2 R482G is the binding of nucleotide.
    • Grant Information:
      G0400631 United Kingdom MRC_ Medical Research Council; United Kingdom CRUK_ Cancer Research UK
    • الرقم المعرف:
      0 (ABCG2 protein, human)
      0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
      0 (ATP-Binding Cassette Transporters)
      0 (Antineoplastic Agents)
      0 (Neoplasm Proteins)
      10028-17-8 (Tritium)
      8L70Q75FXE (Adenosine Triphosphate)
      ZS7284E0ZP (Daunorubicin)
    • الموضوع:
      Date Created: 20080729 Date Completed: 20081003 Latest Revision: 20211020
    • الموضوع:
      20221213
    • الرقم المعرف:
      10.1111/j.1742-4658.2008.06578.x
    • الرقم المعرف:
      18657189