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	Structural basis for the subtype-selectivity of K2.2 channel activators.
Journal, issue, pages	Nat Commun, Vol. 17, Issue 1, Page 531, Year 2026
Publish date	Jan 8, 2026
Authors	Young-Woo Nam / Alena Ramanishka / Yang Xu / Rose Marie Haynes Yasuda / Joshua A Nasburg / Dohyun Im / Meng Cui / K George Chandy / Heike Wulff / Miao Zhang /
PubMed Abstract	Small-conductance (K2.2) and intermediate-conductance (K3.1) Ca-activated K channels are gated by a Ca-calmodulin dependent mechanism. NS309 potentiates the activity of both K2.2 and K3.1, while ...Small-conductance (K2.2) and intermediate-conductance (K3.1) Ca-activated K channels are gated by a Ca-calmodulin dependent mechanism. NS309 potentiates the activity of both K2.2 and K3.1, while rimtuzalcap selectively activates K2.2. Rimtuzalcap has been used in clinical trials for the treatment of spinocerebellar ataxia and essential tremor. We report cryo-electron microscopy structures of NS309-bound K2.2 and K3.1, in addition to structures of rimtuzalcap-bound K2.2 and mutant K3.1_R355K. The different conformations of calmodulin and the cytoplasmic HC helices in the two channels underlie the subtype-selectivity of rimtuzalcap for K2.2. NS309 binds to pre-existing pockets in both channels, while the bulkier rimtuzalcap binds in an induced-fit pocket in K2.2 requiring conformational changes. In K2.2, calmodulin's N-lobes are sufficiently far apart to enable conformational changes to accommodate either NS309 or rimtuzalcap. In K3.1, calmodulin's N-lobes are closer to each other and constrained by K3.1's HC helices, which allows binding of NS309 but not rimtuzalcap. Replacement of arginine-355 in K3.1's HB helix with lysine (K3.1_R355K) allows the binding of rimtuzalcap and renders the mutant channel sensitive to rimtuzalcap. These structures provide a framework for structure-based drug design targeting K2.2 channels.
External links	Nat Commun / PubMed:41507196 / PubMed Central
Methods	EM (single particle)
Resolution	2.96 - 4.73 Å
Structure data	70217 9o85 EMDB-70217, PDB-9o85: Cryo-EM structure of KCa2.2_I/calmodulin channel in complex with rimtuzalcap Method: EM (single particle) / Resolution: 3.13 Å 70240 9o93 EMDB-70240, PDB-9o93: Cryo-EM structure of KCa2.2_II/calmodulin channel in complex with rimtuzalcap Method: EM (single particle) / Resolution: 2.96 Å 70275 9oa8 EMDB-70275, PDB-9oa8: Cryo-EM structure of KCa3.1/calmodulin channel in complex with NS309 Method: EM (single particle) / Resolution: 3.59 Å 72519 9y5q EMDB-72519, PDB-9y5q: Cryo EM structure of KCa3.1_R355K_I/calmodulin channel in complex with rimtuzalcap Method: EM (single particle) / Resolution: 4.73 Å 72841 9ydz EMDB-72841, PDB-9ydz: Cryo EM structure of KCa3.1_R355K_II/calmodulin channel in complex with rimtuzalcap Method: EM (single particle) / Resolution: 3.4 Å
Chemicals	ChemComp-K: Unknown entry PDB-1b92: MOBILITY OF AN HIV-1 INTEGRASE ACTIVE SITE LOOP IS CORRELATED WITH CATALYTIC ACTIVITY ChemComp-CA: Unknown entry ChemComp-HOH: WATER ChemComp-1KP: (3E)-6,7-dichloro-3-(hydroxyimino)-1,3-dihydro-2H-indol-2-one
Source	rattus norvegicus (Norway rat) homo sapiens (human)
Keywords	TRANSPORT PROTEIN / Ion channel / Small-conductance calcium-activated potassium channel / Membrane protein / Intermediate conductance calcium-activated potassium channel / Calmodulin binding protein