8y6h

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

spinqualitylabelsall models 8y6h, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8y6h is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.49Å Ligands: R0Z Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease MDR1_HUMAN Ulcerative colitis. Disease susceptibility is associated with variations affecting the gene represented in this entry. Function MDR1_HUMAN Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. Publication Abstract from PubMed 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 A. In this study, we have obtained a higher resolution (2.5 A) 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. Cryo-EM structure of P-glycoprotein bound to triple elacridar inhibitor molecules.,Hamaguchi-Suzuki N, Adachi N, Moriya T, Yasuda S, Kawasaki M, Suzuki K, Ogasawara S, Anzai N, Senda T, Murata T Biochem Biophys Res Commun. 2024 May 21;709:149855. doi: , 10.1016/j.bbrc.2024.149855. Epub 2024 Mar 28. PMID:38579618 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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