PMID: 11322883Apr 27, 2001Paper

Identification and localization of three photobinding sites of iodoarylazidoprazosin in hamster P-glycoprotein

European Journal of Biochemistry
B IsenbergA Demmer

Abstract

P-glycoprotein is an ATP-dependent drug-efflux pump which can transport a diverse range of structurally and functionally unrelated substrates across the plasma membrane. Overexpression of this protein may result in multidrug resistance and is a major cause of the failure of cancer chemotherapy. The most commonly used photoreactive substrate is iodoarylazidoprazosin. Its binding domains within the P-glycoprotein have so far been inferred from indirect methods such as epitope mapping. In this study, the binding sites were refined and relocalized by direct analysis of photolabeled peptides. P-glycoprotein-containing plasma membrane vesicles of Chinese hamster ovary B30 cells were photoaffinity-labeled with iodoarylazidoprazosin. After chemical cleavage behind tryptophan residues or enzymatic cleavage behind lysine residues, the resulting 125I-labeled peptides were separated by tricine/PAGE and HPLC and subjected to Edman sequencing. The major photoaffinity binding sites of iodoarylazidoprazosin were localized in the amino-acid regions 248-312 [transmembrane segment (TM)4 to TM5], 758-800 (beyond TM7 to beyond TM8) and 1160-1218 (after the Walker A motif of the second nucleotide-binding domain). Therefore the binding pocket of iodo...Continue Reading

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Citations

Nov 22, 2001·Biochemical and Biophysical Research Communications·E J WangW W Johnson
Nov 10, 2006·Journal of Pharmaceutical Sciences·Naoto SuzuyamaTsuyoshi Yokoi
Dec 8, 2009·The FEBS Journal·Emily Crowley, Richard Callaghan
Aug 6, 2004·Biochemical Pharmacology·Cheng WangWang-Fun Fong
Dec 15, 2005·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Suresh V AmbudkarZuben E Sauna
Jun 24, 2020·Journal of Biomolecular Structure & Dynamics·Shirin MollazadehRicardo J Ferreira
Jun 20, 2020·Scientific Reports·Cátia A BonitoDaniel J V A Dos Santos
Feb 4, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jarkko RautioJoseph W Polli

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