Structural characterization of human urea transporters UT-A and UT-B and their inhibition.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37774028.
- Also identified by DOI 10.1126/sciadv.adg8229 and PMC identifier 10541013.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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, UTB<sub>inh</sub>-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.
Medical subject headings
- Membrane Transport Proteins
- Urea