8fhp | pdb_00008fhp

Cryo-EM structure of human NCC (class 3-1)

spinqualitylabelsall models 8fhp, resolution 3.04Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8fhp is a 2 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.04Å Ligands: NA, XZF Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The sodium-chloride cotransporter (NCC) is critical for kidney physiology(1). The NCC has a major role in salt reabsorption in the distal convoluted tubule of the nephron(2,3), and mutations in the NCC cause the salt-wasting disease Gitelman syndrome(4). As a key player in salt handling, the NCC regulates blood pressure and is the target of thiazide diuretics, which have been widely prescribed as first-line medications to treat hypertension for more than 60 years(5-7). Here we determined the structures of human NCC alone and in complex with a commonly used thiazide diuretic using cryo-electron microscopy. These structures, together with functional studies, reveal major conformational states of the NCC and an intriguing regulatory mechanism. They also illuminate how thiazide diuretics specifically interact with the NCC and inhibit its transport function. Our results provide critical insights for understanding the Na-Cl cotransport mechanism of the NCC, and they establish a framework for future drug design and for interpreting disease-related mutations. Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter.,Fan M, Zhang J, Lee CL, Zhang J, Feng L Nature. 2023 Feb;614(7949):788-793. doi: 10.1038/s41586-023-05718-0. Epub 2023 , Feb 15. PMID:36792826 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Solute carrier family 12 3D structures

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