Fig. 3. Crystal structures of SF3B in complex with SD6 and SSE.
a Crystal structure shows that SD6 binds covalently to PHF5A and is engaged in contacts with fewer residues than those binding SSA (depicted and labeled). The water molecule and zinc ions are shown as cyan and magenta spheres, respectively. b Structural comparison between SSA and SD6 in co-crystal structure with the SF3B core. The interactions with chemical groups specific for SSA (i.e., absent from SD6) are shown. c Schematic depiction of the SD6 interaction with residues from the hinged pocket, as observed in the crystal structure. Polar contacts are depicted in blue, whereas the hydrophobic interactions are colored gray. SD6’s functional groups are indicated as boxes. d Crystal structure of SF3BΔBPB in complex with spliceostatin E (SSE). The polder (5.0 σ) electron density maps are displayed around SSE. An anomalous difference map (dark red, 6.0 σ) is contoured around PHF5A’s three zinc ions. Note the presence of ligand density in the SF3B1-PHF5A tunnel corresponding to the distal half of SSE. In contrast, density for the proximal moiety is largely absent, likely because of its flexibility in the absence of covalent coupling to C26-PHF5A. e Structural comparison between SSA and SSE in co-crystal structure with the SF3B core. Note that electron density was observed for the distal moiety of SSE, while the proximal moiety (C1–C10) is likely mobile. The depicted model is based on stereochemistry and space availability in the tunnel.