Fig. 4
From: Structural mechanism of synergistic activation of Aurora kinase B/C by phosphorylated INCENP
VX-680 binding partially disrupts AURKC:INCENP and affects the substrate binding groove. a Crystal structure of AURKC:INCENP:VX-680. AURKC is in magenta for the N-lobe, blue for the C-lobe and orange for the activation loop. INCENP is shown in green, VX-680 in yellow. The parts of the AURKC:INCENP:BRD-7880 structure that differ in position from the structure with VX-680 are shown in grey, illustrating the parts of AURKC:INCENP disrupted by VX-680 binding. b VX-680 binding to AURKC disrupts INCENP binding to the activation loop, disrupting the substrate binding surface. INCENP is shown in green and the part of INCENP not observed in the crystal structure is shown in grey, based on the structure of AURKC:INCENP:BRD-7880. c Binding of INCENP Trp897 to the C-terminal part of AURKC αC is maintained in the presence of VX-680. d A crystal structure of AURKA with BRD-7880 shows that the binding mode of BRD-7880 is conserved. Comparison of this structure with previously published structures of AURKA with VX-680 shows that, as with AURKC, BRD-7880 allows an Aurora kinase conformation resembling the active form exemplified by AURKA:TPX2:ADP, while VX-680 causes a rotation of the N-lobe that disrupts the positions of αB and αC. A 2Fo–Fc electron density map is shown in blue around BRD-7880, contoured at 1.0 σ (0.14 eÅ−3)
