8Y6I

P-glycoprotein in complex with UIC2 Fab and triple elacridar molecules in nanodisc

Summary for 8Y6I

• Entry DOI: 10.2210/pdb8y6i/pdb
• EMDB information: 38987
• Descriptor: ATP-dependent translocase ABCB1,mNeonGreen, UIC2 Fab light chain, UIC2 Fab heavy chain, ... (6 entities in total)
• Functional Keywords: abc transporter, elacridar, p-glycoprotein, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 226316.97

Authors

Hamaguchi-Suzuki, N.,Adachi, N.,Moriya, T.,Kawasaki, M.,Suzuki, K.,Anzai, N.,Senda, T.,Murata, T. (deposition date: 2024-02-02, release date: 2024-04-17)

Primary citation

Hamaguchi-Suzuki, N.,Adachi, N.,Moriya, T.,Yasuda, S.,Kawasaki, M.,Suzuki, K.,Ogasawara, S.,Anzai, N.,Senda, T.,Murata, T.
Cryo-EM structure of P-glycoprotein bound to triple elacridar inhibitor molecules.
Biochem.Biophys.Res.Commun., 709:149855-149855, 2024

PubMed Abstract: 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.

PubMed: 38579618
DOI: 10.1016/j.bbrc.2024.149855

Experimental method

ELECTRON MICROSCOPY (2.54 Å)