Structural Characterization of Human Urea Transporters UT-A and UT-B and Their Inhibition

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Sep 29

PMID 37774028

Authors

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 Durr

Affiliations

Soon will be listed here.

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-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.

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