EMD-16111
Map of Human Urea Transporter UT-A Collected with 0 and 30 Degree Tilts
EMD-16111
Single-particle3.0 Å
Deposition: 10/11/2022Map released: 04/10/2023
Last modified: 11/10/2023
Sample Organism:
Homo sapiens
Sample: Trimer-like complex of Human UT-A
Deposition Authors: Chi G
,
Pike ACW ,
Maclean EM,
Bohstedt T,
Wang D ,
Mckinley G ,
Fernandez-Cid A,
Mukhopadhyay SMM,
Burgess-Brown NA,
Edwards A,
Arrowsmith C,
Bountra C,
Duerr KL
Sample: Trimer-like complex of Human UT-A
Deposition Authors: Chi G
,
Pike ACW ,
Maclean EM,
Bohstedt T,
Wang D ,
Mckinley G ,
Fernandez-Cid A,
Mukhopadhyay SMM,
Burgess-Brown NA,
Edwards A,
Arrowsmith C,
Bountra C,
Duerr KL
Structural characterization of human urea transporters UT-A and UT-B and their inhibition.
Chi G ,
Dietz L ,
Tang H ,
Snee M ,
Scacioc A,
Wang D ,
Mckinley G ,
Mukhopadhyay SMM,
Pike ACW ,
Chalk R,
Burgess-Brown NA,
Timmermans JP ,
van Putte W ,
Robinson CV ,
Durr KL
(2023) Sci Adv , 9 , eadg8229 - eadg8229
,
Dietz L ,
Tang H ,
Snee M ,
Scacioc A,
Wang D ,
Mckinley G ,
Mukhopadhyay SMM,
Pike ACW ,
Chalk R,
Burgess-Brown NA,
Timmermans JP ,
van Putte W ,
Robinson CV ,
Durr KL
(2023) Sci Adv , 9 , eadg8229 - eadg8229
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.
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.