Fig. 5. Structural comparison between covalent and non-covalent modulators.

a Superposition of SF3B^ΔBPB–SSA onto SF3B^ΔBPB–PD. Atoms from the conjugated diene moiety are numbered. PHF5A complexed with SSA is colored brown. b Schematic of the SF3B1-PHF5A pocket with the PB (PDB 6EN4) and the SSA ligands superimposed. SF3B residues contacting SSA are indicated. Residues that also contact PB are circled. Residues involved in polar contacts and hydrophobic interactions with SSA are colored in blue and gray, respectively. c Comparison between SF3B^ΔBPB–SSA, SF3B^ΔBPB–SSE, and SF3B^ΔBPB–PD structures. The crystal structure of isolated E7107 (DB12508) is superimposed on the macrolide ring of PD. PHF5A is not shown for clarity’s sake. d A different view of the superpositions shown in c. PHF5A is depicted in pink.