Figure 5
Crystal structure of the tubulin-jerantinine B acetate (9) complex. (A) Overall view of the T2R-TTL-jerantinine B acetate complex structure. The α- and β-tubulin chains are in dark and light grey ribbon representation, respectively. The tubulin-bound 9 and GTP molecules are represented as green and orange spheres, respectively; (B) Close-up view of the interactions observed between 9 (green) and tubulin (grey). Interacting residues of tubulin are shown in stick representation and are labelled. Oxygen and nitrogen atoms are coloured red and blue, respectively; carbon atoms are in green 9 or grey (tubulin). Secondary structural elements of tubulin are labelled in blue. For simplicity, only α-tubulin residues are indicated with an α; (C) Superimposition of the tubulin-9 (green/grey) and the tubulin-colchicine (pink; PDB ID 4O2B; rmsd of 0.204 Å over 351 Cα-atoms) complex structures. The structures were superimposed onto their β1-tubulin chains; (D) Molecular docking of (−)-jerantinine A (1) in the colchicine binding pocket of tubulin; this pocket is formed by residues in the αT5-loop on α-tubulin, and βH7, βH8, βS8, βS9 and the βT7-loop on β-tubulin. For additional experimental details see the Supporting Information.
