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-Structure paper
タイトル | Cryo-EM structure of P-glycoprotein bound to triple elacridar inhibitor molecules. |
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ジャーナル・号・ページ | Biochem Biophys Res Commun, Vol. 709, Page 149855, Year 2024 |
掲載日 | 2024年5月21日 |
著者 | Norie Hamaguchi-Suzuki / Naruhiko Adachi / Toshio Moriya / Satoshi Yasuda / Masato Kawasaki / Kano Suzuki / Satoshi Ogasawara / Naohiko Anzai / Toshiya Senda / Takeshi Murata / |
PubMed 要旨 | P-glycoprotein (P-gp) is an ATP-binding cassette transporter known for its roles in expelling xenobiotic compounds from cells and contributing to cellular drug resistance through multidrug efflux. ...P-glycoprotein (P-gp) is an ATP-binding cassette transporter known for its roles in expelling xenobiotic compounds from cells and contributing to cellular drug resistance through multidrug efflux. This mechanism is particularly problematic in cancer cells, where it diminishes the therapeutic efficacy of anticancer drugs. P-gp inhibitors, such as elacridar, have been developed to circumvent the decrease in drug efficacy due to P-gp efflux. An earlier study reported the cryo-EM structure of human P-gp-Fab (MRK-16) complex bound by two elacridar molecules, at a resolution of 3.6 Å. In this study, we have obtained a higher resolution (2.5 Å) structure of the P-gp- Fab (UIC2) complex bound by three elacridar molecules. This finding, which exposes a larger space for compound-binding sites than previously acknowledged, has significant implications for the development of more selective inhibitors and enhances our understanding of the compound recognition mechanism of P-gp. |
リンク | Biochem Biophys Res Commun / PubMed:38579618 |
手法 | EM (単粒子) |
解像度 | 2.49 - 2.54 Å |
構造データ | EMDB-38986, PDB-8y6h: EMDB-38987, PDB-8y6i: |
化合物 | ChemComp-R0Z: ChemComp-CLR: ChemComp-3PE: |
由来 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / ABC transporter / elacridar / P-glycoprotein (P糖タンパク質) |