Structural characterization of human urea transporters UT-A and UT-B and their inhibition.
Sci Adv
; 9(39): eadg8229, 2023 09 29.
Article
em En
| MEDLINE
| ID: mdl-37774028
ABSTRACT
In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level and to detail the mechanism of UT-B inhibition by its selective inhibitor, UTBinh-14. High-resolution structures of both transporters establish the structural basis for the inhibitor's selectivity to UT-B, and the identification of multiple binding sites for the inhibitor will aid with the development of drug lead molecules targeting both transporters. Our study also discovers phospholipids associating with the urea transporters by combining structural observations, native MS, and lipidomics analysis. These insights improve our understanding of urea transporter function at a molecular level and provide a blueprint for a structure-guided design of therapeutics targeting these transporters.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Ureia
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article