Article

Structural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantrolene

2024-10-24

Abstract excerpt

Malignant hyperthermia (MH) is a life-threatening pharmacogenetic condition triggered by volatile anesthetics, which activate pathogenic RyR1 mutants. The small molecule therapeutic dantrolene has long been used to treat MH. However, the binding site and mechanism of dantrolene remain unclear. Here, we present cryo-EM structures of RyR1 bound to dantrolene and the MH trigger agent 4-chloro-m-cresol (4CmC), reveali...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 95026b2b-64ae-5543-960e-1036640ea35a
DOI: 10.1101/2024.10.21.619409

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Structural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantroleneDOI 10.1101/2024.10.21.619409Read

Structural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantroleneSemantic proximity Read

Dantrolene inhibition of ryanodine receptor 1 carrying the severe malignant hyperthermia mutation Y522S visualized by cryo-EM.Semantic proximity Read

Optimization of CHARMM force field parameters for ryanodine receptor inhibitory drug dantrolene using FFTK and FFParam.Semantic proximity Read

Molecular mechanism of the severe MH/CCD mutation Y522S in skeletal ryanodine receptor (RyR1) by cryo-EM.Semantic proximity Read

Reduced threshold for store overload-induced Ca2+ release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease.Semantic proximity Read

A novel RyR1 inhibitor prevents and rescues sudden death in a mouse model of malignant hyperthermia and heat strokeSemantic proximity Read

A novel RyR1-selective inhibitor prevents and rescues sudden death in mouse models of malignant hyperthermia and heat stroke.Semantic proximity Read

TRPM8 protein dynamics correlates with ligand structure and cellular functionSemantic proximity Read

Identification of a Binding Site for Small Molecule Inhibitors Targeting Human TRPM4Semantic proximity Read

Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands.Semantic proximity Read

Structural insights into the human P2X1 receptor and ligand interactionsSemantic proximity Read

Mapping Ryanodine Binding Sites in the Pore Cavity of Ryanodine Receptors.Semantic proximity Read