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	Temperature and intrinsic Ca reshape TRPM4 pharmacology.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 33, Issue 6, Page 973-984, Year 2026
Publish date	Jun 9, 2026
Authors	Jinhong Hu / Sofia Ievleva / Sung Jin Park / Junuk Lee / Jie Cheng / Garrett O'Dea / Jiangnan Sheng / Juan Du / Wei Lü /
PubMed Abstract	Proteins operate in dynamic environments where ions, lipids and temperature collectively define their properties, yet most studies rely on simplified conditions that overlook these intrinsic ...Proteins operate in dynamic environments where ions, lipids and temperature collectively define their properties, yet most studies rely on simplified conditions that overlook these intrinsic variables. Here we show two such factors-temperature and Ca-remodel the function and pharmacology of TRPM4, an ion channel implicated in cardiac conduction, immune regulation, cancer and intestinal-fluid homeostasis. At physiological temperature and Ca, TPPO-previously considered a selective TRPM5 inhibitor inactive toward TRPM4-potently activates TRPM4, revealing strong synergy among temperature, Ca and ligand binding. By contrast, Necrocide-1, a necroptotic activator targeting the same binding pocket, defies this logic: it opens TRPM4 without Ca but is antagonized by Ca. Meanwhile, the inhibitors NBA and CBA engage a nearby pocket, locking the channel in a non-conductive pre-open state. Our findings highlight that even rigid binding pockets can exhibit temperature-dependent ligand recognition, revealing hidden pharmacology and informing selective, environment-aware therapeutic strategies.
External links	Nat Struct Mol Biol / PubMed:42265346 / PubMed Central
Methods	EM (single particle)
Resolution	2.51 - 3.26 Å
Structure data	73754 9z1w EMDB-73754, PDB-9z1w: Cryo-EM structure of human TRPM4 channel in complex with calcium and TPPO at 37 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.86 Å 73755 9z1x EMDB-73755, PDB-9z1x: Cryo-EM structure of human TRPM4 channel in the warm conformation in complex with calcium and TPPO at 37 degrees Celsius (monomeric TMD-focused map with best-resolved TPPO density) Method: EM (single particle) / Resolution: 3.0 Å 73756 9z1y EMDB-73756, PDB-9z1y: Cryo-EM structure of human TRPM4 channel in the cold conformation in complex with calcium and TPPO at 37 degrees Celsius (monomeric TMD-focused map with best-resolved TPPO density) Method: EM (single particle) / Resolution: 3.26 Å 73757 9z1z EMDB-73757, PDB-9z1z: Cryo-EM structure of human TRPM4 channel in complex with calcium and TPPO at 18 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.63 Å 73758 9z20 EMDB-73758, PDB-9z20: Cryo-EM structure of human TRPM4 channel in complex with EGTA and TPPO at 37 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.51 Å 73759 9z21 EMDB-73759, PDB-9z21: Cryo-EM structure of human TRPM4 channel in complex with calcium and NC1 at 37 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.83 Å 73760 9z22 EMDB-73760, PDB-9z22: Cryo-EM structure of human TRPM4 channel in complex with EGTA and NC1 at 37 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.58 Å 73761 9z23 EMDB-73761, PDB-9z23: Cryo-EM structure of human TRPM4 channel in complex with calcium and CBA at 37 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.59 Å 73762 9z24 EMDB-73762, PDB-9z24: Cryo-EM structure of human TRPM4 channel in complex with calcium and CBA at 37 degrees Celsius (monomeric TMD-focused map with best-resolved CBA density) Method: EM (single particle) / Resolution: 3.1 Å 73763 9z25 EMDB-73763, PDB-9z25: Cryo-EM structure of human TRPM4 channel in complex with calcium and NBA at 37 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.64 Å 73764 9z26 EMDB-73764, PDB-9z26: Cryo-EM structure of human TRPM4 channel in complex with calcium and NBA at 37 degrees Celsius (monomeric TMD-focused map with best-resolved NBA density) Method: EM (single particle) / Resolution: 2.9 Å 73765 9z27 EMDB-73765, PDB-9z27: Cryo-EM structure of human TRPM4 channel in complex with calcium and CBA and DVT at 37 degrees Celsius (consensus) Method: EM (single particle) / Resolution: 2.76 Å
Chemicals	ChemComp-CA: Unknown entry PDB-1cg5: DEOXY FORM HEMOGLOBIN FROM DASYATIS AKAJEI PDB-1cy8: COMPLEX OF E.COLI DNA TOPOISOMERASE I WITH 5'-THYMIDINE MONOPHOSPHATE AND 3'-THYMIDINE MONOPHOSPHATE PDB-1cz0: INTRON ENCODED HOMING ENDONUCLEASE I-PPOI/DNA COMPLEX LACKING CATALYTIC METAL ION PDB-1h0c: The crystal structure of human alanine:glyoxylate aminotransferase
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / ion channel / TRP channel