Fig. 2: Structure of β-cardiac myosin motor domain complexed to aficamten and Mg.ADP.Vanadate in the PPS state.

a, Overall structure with the different subdomains colored distinctly. Two insets show that both the nucleotide and the drug were rebuilt without ambiguity in the density: the upper inset displays ADP and Vanadate and the lower inset displays aficamten. In both the 2Fo-Fc electron density map is contoured at 1.0 σ of the nucleotide and the drug is shown, demonstrating that these elements have been built without ambiguity. The subdomains are colored distinctly. N-term, N-terminal subdomain. b, Aficamten targets the same pocket as blebbistatin. The side chains of the residues involved in the binding are shown as sticks. c, Zoom in on the coordination of the water involved in the binding of aficamten. The connectors switch-1 (Sw1) and switch-2 (Sw2) are colored distinctly. d, Scheme of the aficamten binding site drawn with LigPlot⁷². e, Sequence alignment of different Homo sapiens class-2 myosin heavy chains: β-cardiac myosin (Card), SMM 2 (SmMyo2), skeletal myosin 2 (SkMyo2). Positions of the residues involved in the binding of aficamten are represented in bold. If the residue is conserved, it is colored red. Non-conserved positions are colored black. Residues involved in a polar interaction are contoured in orange. Residues involved in the coordination of water are contoured in blue.