{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Alam A"],"funding":["Oncosuisse","Swiss National Science Foundation","National Institutes of Health","NIGMS NIH HHS"],"pagination":["753-756"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6800160"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["363(6428)"],"pubmed_abstract":["ABCB1, also known as P-glycoprotein, actively extrudes xenobiotic compounds across the plasma membrane of diverse cells, which contributes to cellular drug resistance and interferes with therapeutic drug delivery. We determined the 3.5-angstrom cryo-electron microscopy structure of substrate-bound human ABCB1 reconstituted in lipidic nanodiscs, revealing a single molecule of the chemotherapeutic compound paclitaxel (Taxol) bound in a central, occluded pocket. A second structure of inhibited, human-mouse chimeric ABCB1 revealed two molecules of zosuquidar occupying the same drug-binding pocket. Minor structural differences between substrate- and inhibitor-bound ABCB1 sites are amplified toward the nucleotide-binding domains (NBDs), revealing how the plasticity of the drug-binding site contr"],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Structural insight into substrate and inhibitor discrimination by human P-glycoprotein."],"pmcid":["PMC6800160"],"funding_grant_id":["P20GM109091","P20 GM109091"],"pubmed_authors":["Broude E","Alam A","Locher KP","Roninson I","Kowal J"],"additional_accession":[]},"is_claimable":false,"name":"Structural insight into substrate and inhibitor discrimination by human P-glycoprotein.","description":"ABCB1, also known as P-glycoprotein, actively extrudes xenobiotic compounds across the plasma membrane of diverse cells, which contributes to cellular drug resistance and interferes with therapeutic drug delivery. We determined the 3.5-angstrom cryo-electron microscopy structure of substrate-bound human ABCB1 reconstituted in lipidic nanodiscs, revealing a single molecule of the chemotherapeutic compound paclitaxel (Taxol) bound in a central, occluded pocket. A second structure of inhibited, human-mouse chimeric ABCB1 revealed two molecules of zosuquidar occupying the same drug-binding pocket. Minor structural differences between substrate- and inhibitor-bound ABCB1 sites are amplified toward the nucleotide-binding domains (NBDs), revealing how the plasticity of the drug-binding site contr","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Feb","modification":"2026-05-04T17:12:43.764Z","creation":"2019-10-30T08:23:06Z"},"accession":"S-EPMC6800160","cross_references":{"pubmed":["30765569"],"doi":["10.1126/science.aav7102"]}}