Work

Unveiling the Structure of PROT and ATB0,+: Unique Members of the Glycine Transporter Subfamily

Year: 2025

Type: article

Abstract: The proline transporter (PROT, SLC6A7) and the neutral and cationic amino acid transporter (ATB0,+, SLC6A14) belong to the glycine transporter subfamily, exhibiting distinct substrate specificities and physiological functions. PROT modulates neurotransmission through proline transport in the brain, while ATB0,+ facilitates nutrient uptake, especially in the gastrointestinal tract. Impaired function of PROT has been associated with neurological disorders, while ATB0,+ overexpression has been linked to cancers. Despite their biological relevance, the pool of known ligands for these transporters is limited, and their exact 3D structures remain unknown. Therefore, we conducted an in silico analysis of PROT and ATB0,+ and compared the obtained results with available literature data on the glycine transporter GlyT1, from the same subfamily. Using homology modelling, docking studies, and molecular dynamics simulations, we investigated the structural properties of PROT and ATB0,+ and described protein–ligand interactions. We pointed crucial residues responsible for ligand binding, including Tyr133, Tyr297, Phe303, and Phe403 in PROT and Trp327, Val128, and Tyr321 in ATB0,+. This work provides new insights into the molecular features of PROT and ATB0,+ transporters, which could support the development of novel transporter inhibitors.

Source: Molecules

DOI: 10.3390/molecules30224412

Authors: Dorota Stary, Marek Bajda

Institutions: Jagiellonian University, University of Würzburg

Language: English

Topic: Amino Acid Enzymes and Metabolism

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,258

Funders: Uniwersytet Jagielloński Collegium Medicum, Deutscher Akademischer Austauschdienst, Julius-Maximilians-Universität Würzburg