Comprehensive characterization of the OCT1 phenylalanine-244-alanine substitution reveals highly substrate-dependent effects on transporter function.

ABSTRACT: 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% of WT activity up to 8-fold increased transport rates. Four percent of substrates showed strongly increased uptake (>200% of WT) whereas 39% showed strongly reduced tran

SUBMITTER: Wittern CI 

PROVIDER: S-EPMC11602988 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature