Fig. 1: The X-ray crystal structure of KY216 in complex with tubulin and the molecular interactions between KY216 and tubulin proteins.

a Chemical structure of KY216. b Overall structure of the complex crystallized (PDB code 8YRK). RB3-SLD is orange; α-tubulin is blue; β-tubulin is pink; TTL is wheat; KY216 is marked with a black box and shown as a yellow sphere. GTP is shown as a green sphere, and GDP is shown as a purple sphere. c The electron cloud density of KY216 is presented at 2mFo-DFC with a contour level of 1.0σ. d The diagram details the molecular interactions between the KY216 (represented by yellow sticks) and the tubulin dimer, with α-tubulin illustrated as a blue cartoon and β-tubulin as a pink cartoon. It highlights one classical hydrogen bond, marked with a cyan dashed line, and three non-classical hydrogen bonds, marked with light green dashed lines. Additionally, one halogen bond is present, marked with a gray dashed line. The corresponding amino acids are represented using their single-letter codes. e Comparison of the binding modes between Podophyllotoxin and KY216. Structures of Tubulin-KY216 (pink cartoon) and Tubulin-podophyllotoxin (PDB code 1SA1, gray cartoon) are superimposed. KY216 (yellow) and podophyllotoxin (green) are shown as rods. f Superimposition of “straight” tubulin (PDB code 7TQY, gray cartoon) and “curved” Tubulin-KY216 (pink cartoon). Black arrows point out the conflict between “straight” tubulin and KY216 (yellow spheres).