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	Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.
Journal, issue, pages	Sci Adv, Vol. 12, Issue 18, Page eaed6472, Year 2026
Publish date	Apr 29, 2026
Authors	Arun Kumar Somavarapu / Jinghua Ge / Christopher M Yengo / Roger Craig / Raul Padron /
PubMed Abstract	Genetic mutations in myosin, the motor protein that powers the heartbeat, are linked to inherited hypertrophic and dilated cardiomyopathies. Mavacamten and omecamtiv mecarbil are therapeutic, myosin- ...Genetic mutations in myosin, the motor protein that powers the heartbeat, are linked to inherited hypertrophic and dilated cardiomyopathies. Mavacamten and omecamtiv mecarbil are therapeutic, myosin-targeted drugs designed to treat these myopathies, but their mechanism of action has remained unclear. Using single-particle cryo-EM, we determined near-atomic resolution structures of wild-type, mavacamten-bound, and omecamtiv mecarbil-bound myosin molecules. Across all conditions, we observe two distinct, alternate conformations of myosin, not previously reported. We show how mavacamten stabilizes one conformation by reinforcing key electrostatic interfaces in the molecule, whereas omecamtiv mecarbil weakens these interfaces, favoring the second structure. This remodeling elucidates previously unclear allosteric mechanisms through which these drugs either inhibit or enhance myosin activity, countering the deleterious impacts of disease. These findings reveal how drugs modulate myosin structure to control cardiac contractility.
External links	Sci Adv / PubMed:42054467 / PubMed Central
Methods	EM (single particle)
Resolution	3.0 - 4.5 Å
Structure data	73268 9yop EMDB-73268, PDB-9yop: Cryo-EM structure of human beta-cardiac myosin in the interacting-heads motif and S2-FH docked state Method: EM (single particle) / Resolution: 3.5 Å 73283 9yp4 EMDB-73283, PDB-9yp4: Cryo-EM structure of human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH docked state Method: EM (single particle) / Resolution: 4.5 Å 73288 9yp9 EMDB-73288, PDB-9yp9: Cryo-EM structure of human beta-cardiac myosin bound to mavacamten in the interacting-heads motif and S2-FH docked state Method: EM (single particle) / Resolution: 3.0 Å 73362 9yr7 EMDB-73362, PDB-9yr7: Cryo-EM structure of human beta-cardiac myosin bound to mavacamten in the interacting-heads motif and S2-FH undocked state Method: EM (single particle) / Resolution: 3.0 Å 73367 9yrg EMDB-73367, PDB-9yrg: Cryo-EM structure of human beta-cardiac myosin in the interacting-heads motif and S2-FH undocked state Method: EM (single particle) / Resolution: 3.2 Å 73368 9yrh EMDB-73368, PDB-9yrh: Cryo-EM structure of human beta-cardiac myosin bound to omecamtiv mecarbil in the interacting-heads motif and S2-FH undocked state Method: EM (single particle) / Resolution: 3.8 Å
Chemicals	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-PO4: PHOSPHATE ION ChemComp-2OW: methyl 4-(2-fluoro-3-{[(6-methylpyridin-3-yl)carbamoyl]amino}benzyl)piperazine-1-carboxylate ChemComp-XB2*: 6-[[(1~{S})-1-phenylethyl]amino]-3-propan-2-yl-1~{H}-pyrimidine-2,4-dione
Source	homo sapiens (human) mus musculus (house mouse) aequorea victoria (jellyfish) saccharomyces cerevisiae (brewer's yeast)
Keywords	CONTRACTILE PROTEIN / Cardiac Myosin / Interacting Heads Motif / Actin Binding / Omecamtiv Mecarbil / Mavacamten