Lucanthone and Its Derivative Hycanthone Inhibit Apurinic Endonuclease-1 (APE1) by Direct Protein Binding
Figure 12
Molecular Dynamics simulation of APE1-bound Lucanthone and Hycanthone.
A: lucanthone (magenta sticks) binds in the hydrophobic pocket of Ape1, represented by its solvent accessible surface. Ape1 interacts with lucanthone mainly via apolar contacts with W280, pi-stacking with F266, and M270. Additionally, a hydrogen bond forms between the carbonyl oxygen and T268. B) Hycanthone (magenta sticks) binds in the DNA groove/hydrophobic pocket of APE1. In addition to apolar contacts and pi-stacking with F266, it forms a hydrogen bond with His309 and coordinates with the APE1-bound magnesium cation (represented as gray sphere).