Lysine 268 adjacent to transmembrane helix 5 of hamster P‐glycoprotein is the major photobinding site of iodomycin in CHO B30 cells

FEBS Open Bio

Burkhard Tümmler¹  Hubert Thole¹  Annette Demmer¹  Manfred Raida² 

[1] Klinische Forschergruppe Klinik für Pädiatrische Pneumologie Allergologie und Neonatologie Medizinische Hochschule Hannover Germany;Singapore Lipidomics Incubator (SLING) Life Sciences Institute National University of Singapore Singapore;

关键词: ABC transporter;    anthracycline;    drug‐binding site;    Edman sequencing;    multidrug resistance;    P‐glycoprotein;   

DOI  :  10.1002/2211-5463.13112

来源: DOAJ

【 摘 要 】

P‐glycoprotein (Pgp) detoxifies cells by exporting hundreds of chemically dissimilar hydrophobic and amphipathic compounds and is implicated in multidrug resistance (MDR) in the treatment of cancers. Photoaffinity labeling of plasma membrane vesicles of MDR CHO B30 cells with the anthracycline [125I]‐iodomycin, subsequent sequential cleavage with BNPS‐skatol and endoproteinase Lys‐C, and the Edman sequencing of the purified photoaffinity‐labeled peptide identified the lysine residue at position 268 in the hamster Pgp primary sequence as the major photobinding site of iodomycin in CHO B30 cells. Lysine 268 is located adjacent to the cytosolic terminus of transmembrane 5. According to thermodynamic and kinetic analyses, this location should present the equilibrium binding site of ATP‐free Pgp for daunomycin and iodomycin in B30 cells.

【 授权许可】

Unknown