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. Author manuscript; available in PMC: 2021 Nov 19.
Published in final edited form as: Cell Chem Biol. 2020 Jul 28;27(11):1347–1358.e5. doi: 10.1016/j.chembiol.2020.07.007

Figure 3 |. Co-crystal structure of ENPP1 and compound 15 reveals molecular determinants of potency.

Figure 3 |

(A) The 3.2 Å crystal structure of compound 15 (green spheres) bound to mouse ENPP1 (gray surface; catalytic and nuclease-like domains). (B) Expanded view of compound 15 (green sticks/spheres) bound in the active site of ENPP1 (gray sticks). Zincs are shown as dark gray spheres. Hydrogen bonds and metal coordination are shown as dashed lines. (C) Chemical structure of compound 15. (D) Schematic drawing of interactions formed between compound 15 (green) and the ENPP1 active site (black). Residues within 5 Å are shown. Metal coordination shown as gray dashed lines, hydrogen bonds shown as black dashed lines, aromatic interactions shown as black wedged lines, and hydrophobic or polar interactions shown as spokes. (E) Overlay of compound 15 (green) with the AMP (orange, PDB 4GTW), both bound to ENPP1. Ligands are shown as sticks/spheres, protein residue D308 is shown as sticks, and water is shown as sticks/spheres. Density for water molecule is present only in AMP-ENPP1 crystal structure. (F) Chemical structure of AMP. See also Figure S1 and Tables S2–S4.