Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Hotspot pocket-based discovery of urea transporter selective inhibitors.
Journal, issue, pages	Nat Commun, Vol. 17, Issue 1, Year 2026
Publish date	Apr 20, 2026
Authors	Lei Liu / Zhi Li / Chao Zhang / Yan Zhang / Zhizhen Huang / Daolai Zhang / Dongfang Li / Juanjuan Zhao / Yuhao Miao / Boyang Cai / Kongkai Zhu / Jin-Peng Sun / Guige Hou / Ying Sun / Baoxue Yang / Xiao Yu / Shenming Huang /
PubMed Abstract	Urea transporter (UT) inhibitors are a promising class of diuretics, as selective inhibitors targeting UT-A subtypes have demonstrated considerable therapeutic potential. Herein, we employ a two- ...Urea transporter (UT) inhibitors are a promising class of diuretics, as selective inhibitors targeting UT-A subtypes have demonstrated considerable therapeutic potential. Herein, we employ a two-round progressive hotspot pocket-based virtual screening approach combined with biological validation to identify M353-0039 as a highly potent and selective inhibitor of UT-A2. We conduct cryo-electron microscopy to solve the structures of UT-A2 bound with the two inhibitors, M353-0039 and E822-1968, at the resolution of 2.7 Å and 2.9 Å respectively, and elucidate the structural mechanism underlying the superior efficacy and selectivity of M353-0039. Compared with the inhibitor HQA2 and E822-1968, M353-0039 occupies a deeper binding pocket and forms more interactions with UT-A2, thus leading to greater inhibitory potency. We demonstrate that the selectivity of M353-0039 is driven by the nonconserved residues C285 and G322 within the "T-T" subpocket of UT-A2. Finally, we validate the selective effects of M353-0039 in inhibiting UT-A2 function both in mouse models and hepatic cell. These findings not only identify a selective inhibitor as a tool that can be applied to elucidate the unique physiological roles of UT-A2 but also provide an available method for efficiently developing UT-A-selective inhibitors with potent activity as the next-generation diuretics.
External links	Nat Commun / PubMed:42009654 / PubMed Central
Methods	EM (single particle)
Resolution	2.7 - 2.9 Å
Structure data	65636 9w4k EMDB-65636, PDB-9w4k: Cryo-EM structure of inhibitor E822-1968 bound human urea transporter A2. Method: EM (single particle) / Resolution: 2.9 Å 65637 9w4l EMDB-65637, PDB-9w4l: Cryo-EM structure of inhibitor M353-0039 bound urea transporter A2. Method: EM (single particle) / Resolution: 2.7 Å
Chemicals	PDB-1eu8: STRUCTURE OF TREHALOSE MALTOSE BINDING PROTEIN FROM THERMOCOCCUS LITORALIS PDB Unreleased entry PDB-1eu9: PROX, PERIPLASMIC BINDING PROTEIN FROM E.COLI IN COMPLEX WITH GLYCINE BETAINE
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / Urea transporter