Figure 5

Mode of interaction of GF with tubulin. (A) Structure of GF. The conformation of the O-Me groups are chosen arbitrarily. Color code: carbon, blue; oxygen, red; hydrogen, grey; chlorine, green. (B) Cartoon rendering of the αβ tubulin heterodimer (PDB id 1TVK) showing the location of the binding sites for colchicine, paclitaxel and vinblastine (purple), GTP and GDP (black) and GF (blue). The "upper" domain is α tubulin and the "lower" domain is β tubulin. In this view, GTP and GDP are partly hidden. Vinblastine binds at the inter-dimer (αβ)-interface and hence, is shown both at the top and bottom. Colchicine binds at the intra-dimer interface (αβ) and paclitaxel binds to the β-subunit. The binding sites for GF, one at the interface (site A) and the other overlapping with that of paclitaxel (site B), are predicted by docking; all others are based on X-ray crystallographic studies. (C) and (D) Representative binding modes of GF in site A (C) and site B (D) obtained by docking. Atoms are colored by element type except for carbon (cyan for GF and grey for binding site residues). Hydrophobic residues constituting the binding pocket and polar residues within 3 Å of GF are shown.