Extended Data Fig. 1: Natural and semisynthetic streptogramins and their molecular mechanisms of action and resistance.

a, Selected natural and semisynthetic streptogramin analogues. Modifications installed by semisynthesis are highlighted in blue. b, 2.5-Å cryo-EM structure of VM2 bound to the 50S subunit of the E. coli ribosome. Coulomb potential density is contoured in dark blue at 4.0σ and light grey at 1.0σ. Atom colouring of VM2 mirrors the building blocks used in its synthesis (see Fig. 2). c, Binding interactions between VM2 and residues in the ribosomal binding site. d, X-ray crystal structure VM1 bound to the resistance protein VatA (PDB ID: 4HUS). e, Binding interactions between VM1 and VatA, highlighting the extensive hydrophobic interactions at C3–C6. Acetylation occurs at the C14 alcohol. f, g, Conformational energy of VM2 showing contributions on a per atom basis when refined with standard CIF-based restraints generated by ‘phenix.eLBOW’ (f) and when refined with OPLS3e/VSGB2.1 force field (g). Colour indicates low strain (green, −14 kcal mol⁻¹) up to high strain (red, 10 kcal mol⁻¹), with total conformational energy of 39.5 kcal mol⁻¹ (f) and −88.3 (g). Hydrogens were added and optimized with fixed heavy atoms for the CIF-based refined conformation using ‘prepwizard’; the PHENIX-OPLS3e/VSGB2.1 refined conformation was taken as is. Energies were calculated using Prime and per atom contribution visualized using Maestro’s prime energy visualization.