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. 2022 Aug 15;13:4785. doi: 10.1038/s41467-022-32436-4

Fig. 4. Crystallographic analyses reveal that the S280F substitution affects the dimer-interface and active site of IDH1 variants.

Fig. 4

a Ribbon view from a crystal structure of R132C/S280F (PDB: 7PJM, 2.1 Å resolution). As observed in the asymmetric unit, an apparent dimer is formed by chain A (wheat) and chain B (green). Orange circles: active sites with 2-OG, NADPH, and calcium. L1 loop: violet. b Close-up view with a Polder omit map (blue mesh, contour 3.0 σ) showing 2-OG, NADPH, and calcium. The L1 loop covering the dimer-interface is in violet. Black circle: dimer-interface with a Polder omit map (blue mesh, contour: 3.0 σ) showing F280 (cyan). c View of the dimer-interface highlighting hydrophobic interactions between W124 (L1), F280 (cyan, α10), and W267 in both monomers. d View of the metal-binding site. The calcium-binding residues D252 (monomer 1, wheat, α9), D275 and D279 (monomer 2, green, α10) are shown. e Ribbon view from a crystal structure of R132C/S280F (PDB: 7PJN), 2.45 Å resolution) complexed with 2 NADPH and 2 DS-1001B (orange) molecules; the enzyme is likely in an open inactive conformation. An apparent dimer is formed by chain B (wheat) and chain C (green), as observed in the asymmetric unit. DS-1001B binds at the dimer-interface (black circle). f Polder omit map (blue mesh, contour: 3.0 σ) showing DS-1001B and residue F280 (cyan) in the dimer-interface. Note that the L1 loop (violet) covers the dimer-interface.