Fig. 4

Crystal structure of PML^VG. a Overall structure of PML^VG colored by sequence ranging from the N-terminus (blue) to the C-terminus (orange). α-Helices are labeled according to wild-type PML [43]. Lid region mutations from directed evolution are shown as red sticks and indicated with arrows. The active-site catalytic triad amino acids are labeled and shown in sticks with the carbons colored in green and the remaining atoms colored by element. A single calcium ion is colored as a magenta sphere. The two MPD molecules in the active site are shown in sticks and colored gray. b Alignment of PML^VG (yellow) to inhibitor-bound PML (PDBID: 4GXN) [43] (cyan). The DEP inhibitor is labeled and shown as sticks with the carbons colored in green and the remaining atoms colored by element. The major difference in the structure of the α6 helix between PML (orange) and PML^VG (red) is highlighted in the red box. c Close-up view showing the shift of PML^VG α6 hydrophobic patch toward the active site and the loop region connecting helices α5 and α6