SLC14A1 / UT1 / UT-B / Urea Transporter / Inhibitor / Solute Carrier / TRANSPORT PROTEIN
機能・相同性
機能・相同性情報
urea channel activity / urea transport / Transport of bile salts and organic acids, metal ions and amine compounds / urea transmembrane transport / urea transmembrane transporter activity / water transmembrane transporter activity / establishment of localization in cell / transmembrane transport / basolateral plasma membrane / plasma membrane 類似検索 - 分子機能
ジャーナル: Sci Adv / 年: 2023 タイトル: Structural characterization of human urea transporters UT-A and UT-B and their inhibition. 著者: Gamma Chi / Larissa Dietz / Haiping Tang / Matthew Snee / Andreea Scacioc / Dong Wang / Gavin Mckinley / Shubhashish M M Mukhopadhyay / Ashley C W Pike / Rod Chalk / Nicola A Burgess-Brown / ...著者: Gamma Chi / Larissa Dietz / Haiping Tang / Matthew Snee / Andreea Scacioc / Dong Wang / Gavin Mckinley / Shubhashish M M Mukhopadhyay / Ashley C W Pike / Rod Chalk / Nicola A Burgess-Brown / Jean-Pierre Timmermans / Wouter van Putte / Carol V Robinson / Katharina L Dürr / 要旨: 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, ...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, UTB-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.