%0 Journal Article
%A Wittern, Carla Isabel
%A Schröder, Sophie
%A Jensen, Ole
%A Brockmöller, Jürgen
%A Gebauer, Lukas
%T Comprehensive characterization of the OCT1 phenylalanine-244-alanine substitution reveals highly substrate-dependent effects on transporter function.
%J The journal of biological chemistry
%V 300
%N 11
%@ 0021-9258
%C Bethesda, Md.
%I Soc.
%M DZNE-2024-01388
%P 107835
%D 2024
%Z ISSN 0021-9258 not unique: **2 hits**.
%X Organic cation transporters (OCTs) can transport structurally highly diverse substrates. The molecular basis of this extensive polyspecificity has been further elucidated by cryo-EM. Apparently, in addition to negatively charged amino acids, aromatic residues may contribute to substrate binding and substrate selectivity. In this study, we provide a comprehensive characterization of phenylalanine 244 in OCT1 function. We analyzed the uptake of 144 OCT1 substrates for the phenylalanine 244 to alanine substitution compared to WTOCT1. This substitution had highly substrate-specific effects ranging from transport reduced to 10
%K Humans
%K Phenylalanine: metabolism
%K Phenylalanine: chemistry
%K Amino Acid Substitution
%K Substrate Specificity
%K HEK293 Cells
%K Alanine: metabolism
%K Alanine: chemistry
%K Kinetics
%K Biological Transport
%K Organic Cation Transporter 1: metabolism
%K Organic Cation Transporter 1: genetics
%K Organic Cation Transporter 1: chemistry
%K alanine mutagenesis (Other)
%K binding pocket (Other)
%K inhibition (Other)
%K organic cation transporter 1 (Other)
%K polyspecificity (Other)
%K site-directed mutagenesis (Other)
%K transport (Other)
%K Phenylalanine (NLM Chemicals)
%K Alanine (NLM Chemicals)
%K Organic Cation Transporter 1 (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39342994
%2 pmc:PMC11602988
%R 10.1016/j.jbc.2024.107835
%U https://pub.dzne.de/record/273914