{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pedersen CN"],"funding":["Aarhus Universitets Forskningsfond","NIDA NIH HHS","Danish Ministry for Research and Higher Education","NIMH NIH HHS","NCI NIH HHS","National Institutes of Health","Novo Nordisk Fonden","Lundbeck Foundation","NIH HHS"],"pagination":["2043-2055"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11449642"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["168(9)"],"pubmed_abstract":["The regulation of dopamine (DA) removal from the synaptic cleft is a crucial process in neurotransmission and is facilitated by the sodium- and chloride-coupled dopamine transporter DAT. Psychostimulant drugs, cocaine, and amphetamine, both block the uptake of DA, while amphetamine also triggers the release of DA. As a result, they prolong or even amplify neurotransmitter signaling. Atypical inhibitors of DAT lack cocaine-like rewarding effects and offer a promising strategy for the treatment of drug use disorders. Here, we present the 3.2 Å resolution cryo-electron microscopy structure of the Drosophila melanogaster dopamine transporter (dDAT) in complex with the atypical non-competitive inhibitor AC-4-248. The inhibitor partially binds at the central binding site, extending into the extr"],"journal":["Journal of neurochemistry"],"pubmed_title":["Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site."],"pmcid":["PMC11449642"],"funding_grant_id":["P30 CA010815-53","R01 DA051205","AUFF‐E‐2022‐9‐24","NNF19OC0054875","R310‐2018‐3713","R01 DA051205-03","P30 CA010815","S10OD030245-01","R346-2020-1944","MH106912","R01 DA051205‐03","S10 OD030245","MH121453","5072-00025B","NNF18OC0032608","R01 MH106912","R56 MH121453","P30 CA010815‐53","S10OD030245‐01","R310-2018-3713","NNF18OC0054875","AUFF-E-2022-9-24","R368-2021-522","R368‐2021‐522"],"pubmed_authors":["Pedersen CN","Neumann CMT","Desdorf LM","Akunuri R","Mortensen OV","Schiott B","Yang F","Ita S","Trampari S","Salvino JM","Shahsavar A","Xu Y","Nissen P"],"additional_accession":[]},"is_claimable":false,"name":"Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site.","description":"The regulation of dopamine (DA) removal from the synaptic cleft is a crucial process in neurotransmission and is facilitated by the sodium- and chloride-coupled dopamine transporter DAT. Psychostimulant drugs, cocaine, and amphetamine, both block the uptake of DA, while amphetamine also triggers the release of DA. As a result, they prolong or even amplify neurotransmitter signaling. Atypical inhibitors of DAT lack cocaine-like rewarding effects and offer a promising strategy for the treatment of drug use disorders. Here, we present the 3.2 Å resolution cryo-electron microscopy structure of the Drosophila melanogaster dopamine transporter (dDAT) in complex with the atypical non-competitive inhibitor AC-4-248. The inhibitor partially binds at the central binding site, extending into the extr","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-05-29T11:34:19.236Z","creation":"2026-04-08T04:30:13.681Z"},"accession":"S-EPMC11449642","cross_references":{"pubmed":["39010681"],"doi":["10.1111/jnc.16179"]}}