8xdc | pdb_00008xdc

Cryo-EM structure of human urea transporter A2.

spinqualitylabelsall models 8xdc, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8xdc is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: A1LVA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UT2_HUMAN Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism. Mediates the transport of urea driven by a concentration gradient across the cell membrane of the kidney inner medullary collecting duct which is critical to the urinary concentrating mechanism. Publication Abstract from PubMed 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(Pb)-T(5b)-T(5a)-Q(Pa) 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. Structural insights into the mechanisms of urea permeation and distinct inhibition modes of urea transporters.,Huang SM, Huang ZZ, Liu L, Xiong MY, Zhang C, Cai BY, Wang MW, Cai K, Jia YL, Wang JL, Zhang MH, Xie YH, Li M, Zhang H, Weng CH, Wen X, Li Z, Sun Y, Yi F, Yang Z, Xiao P, Yang F, Yu X, Tie L, Yang BX, Sun JP Nat Commun. 2024 Nov 26;15(1):10226. doi: 10.1038/s41467-024-54305-y. PMID:39587082 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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