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8XDD

Cryo-EM structure of human urea transporter A2.

Summary for 8XDD
Entry DOI10.2210/pdb8xdd/pdb
EMDB information38274
DescriptorUrea transporter 2, 8-hydroxyquinoline-2-carboxylic acid, 1-(3-methoxyphenyl)methanamine (3 entities in total)
Functional Keywordsurea transporter, membrane protein
Biological sourceHomo sapien
Total number of polymer chains3
Total formula weight131238.40
Authors
Huang, S.,Liu, L.,Sun, J. (deposition date: 2023-12-10, release date: 2024-12-04)
Primary citationHuang, S.M.,Huang, Z.Z.,Liu, L.,Xiong, M.Y.,Zhang, C.,Cai, B.Y.,Wang, M.W.,Cai, K.,Jia, Y.L.,Wang, J.L.,Zhang, M.H.,Xie, Y.H.,Li, M.,Zhang, H.,Weng, C.H.,Wen, X.,Li, Z.,Sun, Y.,Yi, F.,Yang, Z.,Xiao, P.,Yang, F.,Yu, X.,Tie, L.,Yang, B.X.,Sun, J.P.
Structural insights into the mechanisms of urea permeation and distinct inhibition modes of urea transporters.
Nat Commun, 15:10226-10226, 2024
Cited by
PubMed Abstract: Urea's transmembrane transport through urea transporters (UT) is a fundamental physiological behavior for life activities. Here, we present 11 cryo-EM structures of four UT members in resting states, urea transport states, or inactive states bound with synthetic competitive, uncompetitive or noncompetitive inhibitor. Our results indicate that the binding of urea via a conserved urea recognition motif (URM) and the urea transport via H-bond transfer along the Q-T-T-Q motif among different UT members. Moreover, distinct binding modes of the competitive inhibitors 25a and ATB3, the uncompetitive inhibitor CF11 and the noncompetitive inhibitor HQA2 provide different mechanisms for blocking urea transport and achieved selectivity through L-P pocket, UCBP region and SCG pocket, respectively. In summary, our study not only allows structural understanding of urea transport via UTs but also afforded a structural landscape of hUT-A2 inhibition by competitive, uncompetitive and noncompetitive inhibitors, which may facilitate developing selective human UT-A inhibitors as a new class of salt-sparing diuretics.
PubMed: 39587082
DOI: 10.1038/s41467-024-54305-y
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3 Å)
Structure validation

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