Structural characterization of human urea transporters UT-A and UT-B and their inhibition

• DOI: 10.1126/sciadv.adg8229
• Publication Date: 2023-09-29T17:58:44Z
• Authors: Gamma Chi; Larissa Dietz; Haiping Tang; Matthew Snee; Andreea Scacioc; Dong Wang; Gavin Mckinley; Shubhashish M. M....; Ashley C. W. Pike; Rod Chalk; Nicola A. Burgess...; Jean-Pierre Timme...; Wouter van Putte; Carol V. Robinson; Katharina L. Dürr
• Keywords: Urea Transporters; Chemistry; Binding Sites; Humans; Membrane Transport Proteins; Urea; Human medicine; Biomedicine and Life Sciences; Biology; 3. Good health

In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level detail mechanism inhibition by its selective inhibitor, UTBinh-14. High-resolution both establish structural basis for inhibitor's selectivity UT-B, identification multiple binding sites inhibitor will aid with development drug lead molecules targeting transporters. Our study also discovers phospholipids associating combining observations, native MS, lipidomics analysis. These insights improve our understanding transporter function a provide blueprint structure-guided design therapeutics these