Ilgü, HüseyinHüseyinIlgüJeckelmann, Jean-MarcJean-MarcJeckelmannColas, ClaireClaireColasUcurum Fotiadis, ZöhreZöhreUcurum FotiadisSchlessinger, AvnerAvnerSchlessingerFotiadis, Dimitrios JoséDimitrios JoséFotiadis2024-10-072024-10-072018-03-20https://boris-portal.unibe.ch/handle/20.500.12422/62734The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting s indicated stabilization of AdiC variants upon ligand binding, in which s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.en">l-arginine/agmatine transporter ">l-type amino acid transporter AdiC LAT1 acid resistance cancer metabolism enterobacteria melting temperature thermostability500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healtharticle10.7892/boris.1244912955843010.3390/ijms19030918