Matches in SemOpenAlex for { <https://semopenalex.org/work/W2322796880> ?p ?o ?g. }
- W2322796880 endingPage "339" @default.
- W2322796880 startingPage "334" @default.
- W2322796880 abstract "The serotonin transporter (SERT) terminates serotonergic signalling through the sodium- and chloride-dependent reuptake of neurotransmitter into presynaptic neurons. SERT is a target for antidepressant and psychostimulant drugs, which block reuptake and prolong neurotransmitter signalling. Here we report X-ray crystallographic structures of human SERT at 3.15 Å resolution bound to the antidepressants (S)-citalopram or paroxetine. Antidepressants lock SERT in an outward-open conformation by lodging in the central binding site, located between transmembrane helices 1, 3, 6, 8 and 10, directly blocking serotonin binding. We further identify the location of an allosteric site in the complex as residing at the periphery of the extracellular vestibule, interposed between extracellular loops 4 and 6 and transmembrane helices 1, 6, 10 and 11. Occupancy of the allosteric site sterically hinders ligand unbinding from the central site, providing an explanation for the action of (S)-citalopram as an allosteric ligand. These structures define the mechanism of antidepressant action in SERT, and provide blueprints for future drug design." @default.
- W2322796880 created "2016-06-24" @default.
- W2322796880 creator A5008623516 @default.
- W2322796880 creator A5017505330 @default.
- W2322796880 creator A5088125571 @default.
- W2322796880 date "2016-04-06" @default.
- W2322796880 modified "2023-10-10" @default.
- W2322796880 title "X-ray structures and mechanism of the human serotonin transporter" @default.
- W2322796880 cites W1521210328 @default.
- W2322796880 cites W1547089995 @default.
- W2322796880 cites W1579841613 @default.
- W2322796880 cites W168654846 @default.
- W2322796880 cites W1908164157 @default.
- W2322796880 cites W1969206393 @default.
- W2322796880 cites W1970124769 @default.
- W2322796880 cites W1974260392 @default.
- W2322796880 cites W1975304761 @default.
- W2322796880 cites W1980784555 @default.
- W2322796880 cites W1982053398 @default.
- W2322796880 cites W1982891627 @default.
- W2322796880 cites W1985176332 @default.
- W2322796880 cites W1994458658 @default.
- W2322796880 cites W2000904449 @default.
- W2322796880 cites W2004278098 @default.
- W2322796880 cites W2018008180 @default.
- W2322796880 cites W2020717114 @default.
- W2322796880 cites W2020727025 @default.
- W2322796880 cites W2024340541 @default.
- W2322796880 cites W2028353138 @default.
- W2322796880 cites W2030224254 @default.
- W2322796880 cites W2037407420 @default.
- W2322796880 cites W2046376309 @default.
- W2322796880 cites W2049868296 @default.
- W2322796880 cites W2051918534 @default.
- W2322796880 cites W2052745304 @default.
- W2322796880 cites W2057456595 @default.
- W2322796880 cites W2058981075 @default.
- W2322796880 cites W2061108756 @default.
- W2322796880 cites W2065283382 @default.
- W2322796880 cites W2065861447 @default.
- W2322796880 cites W2077531668 @default.
- W2322796880 cites W2077681127 @default.
- W2322796880 cites W2079507733 @default.
- W2322796880 cites W2079704116 @default.
- W2322796880 cites W2080766585 @default.
- W2322796880 cites W2081863829 @default.
- W2322796880 cites W2082229175 @default.
- W2322796880 cites W2084290194 @default.
- W2322796880 cites W2086004174 @default.
- W2322796880 cites W2091649030 @default.
- W2322796880 cites W2096242757 @default.
- W2322796880 cites W2096644570 @default.
- W2322796880 cites W2101886959 @default.
- W2322796880 cites W2104622728 @default.
- W2322796880 cites W2115620372 @default.
- W2322796880 cites W2117003397 @default.
- W2322796880 cites W2120496470 @default.
- W2322796880 cites W2129495111 @default.
- W2322796880 cites W2135190897 @default.
- W2322796880 cites W2139600517 @default.
- W2322796880 cites W2154197653 @default.
- W2322796880 cites W2162746575 @default.
- W2322796880 cites W2163341755 @default.
- W2322796880 cites W2171043072 @default.
- W2322796880 cites W2215904362 @default.
- W2322796880 cites W4233693399 @default.
- W2322796880 cites W4248872320 @default.
- W2322796880 cites W2394944284 @default.
- W2322796880 doi "https://doi.org/10.1038/nature17629" @default.
- W2322796880 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4898786" @default.
- W2322796880 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27049939" @default.
- W2322796880 hasPublicationYear "2016" @default.
- W2322796880 type Work @default.
- W2322796880 sameAs 2322796880 @default.
- W2322796880 citedByCount "478" @default.
- W2322796880 countsByYear W23227968802016 @default.
- W2322796880 countsByYear W23227968802017 @default.
- W2322796880 countsByYear W23227968802018 @default.
- W2322796880 countsByYear W23227968802019 @default.
- W2322796880 countsByYear W23227968802020 @default.
- W2322796880 countsByYear W23227968802021 @default.
- W2322796880 countsByYear W23227968802022 @default.
- W2322796880 countsByYear W23227968802023 @default.
- W2322796880 crossrefType "journal-article" @default.
- W2322796880 hasAuthorship W2322796880A5008623516 @default.
- W2322796880 hasAuthorship W2322796880A5017505330 @default.
- W2322796880 hasAuthorship W2322796880A5088125571 @default.
- W2322796880 hasBestOaLocation W23227968802 @default.
- W2322796880 hasConcept C12554922 @default.
- W2322796880 hasConcept C166342909 @default.
- W2322796880 hasConcept C16696662 @default.
- W2322796880 hasConcept C169760540 @default.
- W2322796880 hasConcept C170493617 @default.
- W2322796880 hasConcept C185592680 @default.
- W2322796880 hasConcept C2775864247 @default.
- W2322796880 hasConcept C2776219046 @default.
- W2322796880 hasConcept C2777490545 @default.
- W2322796880 hasConcept C2778897192 @default.