Fig. 5 | Nature Communications

Fig. 5

From: Structural mechanism of synergistic activation of Aurora kinase B/C by phosphorylated INCENP

Fig. 5

BRD-7880 binding to AURKC:INCENP. a BRD-7880 forms a single hydrogen bond to the kinase hinge region from its benzo−1,3-dioxole moiety, and multiple hydrogen bonds to the P-loop (Lys53) and to Lys72 and Glu91. A 2Fo-Fc electron density map is shown in green around BRD-7880, contoured at 1.0 σ (0.4 eÅ-3) b The central 8-membered ring of BRD-7880 allows excellent shape complementarity to the ATP-binding site of AURKC. c Isothermal titration calorimetry confirmed BRD-7880 has significantly higher affinity for AURKB:INCENP over AURKA, due to more favourable entropy of binding (Supplementary Table 2). d Selectivity of BRD-7880 for AURKB:INCENP over AURKA:TPX2 is increased due to a non-ideal interaction, most likely the forced, possibly partial, dissociation of TPX2 from AURKA upon BRD-7880 binding. e Chemical structure of BRD-7880. f BRD-7880 has slow binding kinetics with AURKB:INCENP, with the long half-life of dissociation contributing to its potent binding. g BRD-7880 binds to AURKC:INCENP and AURKA in the same conformation, with the active site residues of AURKA adopting the same conformations as those of AURKC, with the exception of the DFG motif (residues 274 to 276 of AURKA). AURKC is shown in blue with bound BRD-7880 in yellow, and AURKA is shown in green

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