9PIFSummary for 9PIF
| Entry DOI | 10.2210/pdb9pif/pdb |
| EMDB information | 71665 |
| Descriptor | Solute carrier family 12 member 3, Solute carrier family 12 member 2, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total) |
| Functional Keywords | membrane transporter, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 221196.54 |
| Authors | |
| Primary citation | Lee, C.L.,Zhang, J.,Feng, L. Molecular mechanisms of thiazide-like diuretics-mediated inhibition of the human Na-Cl cotransporter. Nat Commun, 16:7740-7740, 2025 Cited by PubMed Abstract: Thiazide-type and thiazide-like diuretics are structurally distinct first-line antihypertensive drugs that target the sodium-chloride cotransporter (NCC) in the kidney. Thiazide-like diuretics are reported to have better cardioprotective effects than thiazide-type diuretics, but whether this is due to differences in NCC-inhibition mechanisms, if there is any, remains unclear. To understand the molecular mechanisms of NCC inhibition by thiazide-like diuretics, we determine the structures of human NCC (hNCC) bound to two of the most widely used thiazide-like diuretics, chlorthalidone and indapamide, using cryogenic electron microscopy (cryo-EM). Structural analyses reveal shared features and distinctions between NCC-inhibition by thiazide-like and thiazide-type diuretics. Furthermore, structural comparisons allow us to identify polymorphisms in hNCC that have substantial differential effects on the potencies of specific thiazide-like and thiazide-type diuretics. Our work provides important insights into the molecular pharmacology of NCC and a blueprint for developing precision medicine to manage hypertension with thiazide-like and thiazide-type diuretics. PubMed: 40830368DOI: 10.1038/s41467-025-62714-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.24 Å) |
Structure validation
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