% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Gabriel:615561,
author = {Gabriel, Florian and Spriestersbach, Lea and Fuhrmann,
Antonia and Jungnickel, Katharina E. J. and Mostafavi,
Siavash and Pardon, Els and Steyaert, Jan and Löw,
Christian},
title = {{S}tructural basis of thiamine transport and drug
recognition by {SLC}19{A}3},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {PUBDB-2024-06168},
pages = {8542},
year = {2024},
note = {FG (grant numbers INST 152/772-1 | 152/774-1 | 152/775-1 |
152/776-1 | 152/777-1 FUGG},
abstract = {Thiamine (vitamin B1) functions as an essential coenzyme in
cells. Humans and other mammals cannot synthesise this
vitamin de novo and thus have to take it up from their diet.
Eventually, every cell needs to import thiamine across its
plasma membrane, which is mainly mediated by the two
specific thiamine transporters SLC19A2 and SLC19A3. Loss of
function mutations in either of these transporters lead to
detrimental, life-threatening metabolic disorders. SLC19A3
is furthermore a major site of drug interactions. Many
medications, including antidepressants, antibiotics and
chemotherapeutics are known to inhibit this transporter,
with potentially fatal consequences for patients. Despite a
thorough functional characterisation over the past two
decades, the structural basis of its transport mechanism and
drug interactions has remained elusive. Here, we report
seven cryo-electron microscopy (cryo-EM) structures of the
human thiamine transporter SLC19A3 in complex with various
ligands. Conformation-specific nanobodies enable us to
capture different states of SLC19A3’s transport cycle,
revealing the molecular details of thiamine recognition and
transport. We identify seven previously unknown drug
interactions of SLC19A3 and present structures of the
transporter in complex with the inhibitors fedratinib,
amprolium and hydroxychloroquine. These data allow us to
develop an understanding of the transport mechanism and
ligand recognition of SLC19A3.},
cin = {CSSB-EMBL-CL},
ddc = {500},
cid = {I:(DE-H253)CSSB-EMBL-CL-20210806},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39358356},
UT = {WOS:001327144400015},
doi = {10.1038/s41467-024-52872-8},
url = {https://bib-pubdb1.desy.de/record/615561},
}