TY  - JOUR
AU  - Wittern, Carla Isabel
AU  - Schröder, Sophie
AU  - Jensen, Ole
AU  - Brockmöller, Jürgen
AU  - Gebauer, Lukas
TI  - Comprehensive characterization of the OCT1 phenylalanine-244-alanine substitution reveals highly substrate-dependent effects on transporter function.
JO  - The journal of biological chemistry
VL  - 300
IS  - 11
SN  - 0021-9258
CY  - Bethesda, Md.
PB  - Soc.
M1  - DZNE-2024-01388
SP  - 107835
PY  - 2024
N1  - ISSN 0021-9258 not unique: **2 hits**.
AB  - 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
KW  - Humans
KW  - Phenylalanine: metabolism
KW  - Phenylalanine: chemistry
KW  - Amino Acid Substitution
KW  - Substrate Specificity
KW  - HEK293 Cells
KW  - Alanine: metabolism
KW  - Alanine: chemistry
KW  - Kinetics
KW  - Biological Transport
KW  - Organic Cation Transporter 1: metabolism
KW  - Organic Cation Transporter 1: genetics
KW  - Organic Cation Transporter 1: chemistry
KW  - alanine mutagenesis (Other)
KW  - binding pocket (Other)
KW  - inhibition (Other)
KW  - organic cation transporter 1 (Other)
KW  - polyspecificity (Other)
KW  - site-directed mutagenesis (Other)
KW  - transport (Other)
KW  - Phenylalanine (NLM Chemicals)
KW  - Alanine (NLM Chemicals)
KW  - Organic Cation Transporter 1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39342994
C2  - pmc:PMC11602988
DO  - DOI:10.1016/j.jbc.2024.107835
UR  - https://pub.dzne.de/record/273914
ER  -