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Crystal structure of human aurora B in complex with INCENP and VX-680.


ABSTRACT: We present the structure of the human Aurora B kinase domain in complex with the C-terminal Aurora-binding region of human INCENP and the Aurora kinase inhibitor VX-680. The structure unexpectedly reveals a dimeric arrangement of the Aurora B:INCENP complex, which was confirmed to exist in solution by analytical ultracentrifugation. The dimerization involves a domain swap of the activation loop, resulting in a different conformation of the DFG motif as compared to that seen in other kinase complexes with VX-680. The binding of INCENP differs significantly from that seen in the Xenopus laevis Aurora B:INCENP complex currently used as a model for structure-based design for this important oncology target.

SUBMITTER: Elkins JM 

PROVIDER: S-EPMC3621106 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Crystal structure of human aurora B in complex with INCENP and VX-680.

Elkins Jonathan M JM   Santaguida Stefano S   Musacchio Andrea A   Knapp Stefan S  

Journal of medicinal chemistry 20120904 17


We present the structure of the human Aurora B kinase domain in complex with the C-terminal Aurora-binding region of human INCENP and the Aurora kinase inhibitor VX-680. The structure unexpectedly reveals a dimeric arrangement of the Aurora B:INCENP complex, which was confirmed to exist in solution by analytical ultracentrifugation. The dimerization involves a domain swap of the activation loop, resulting in a different conformation of the DFG motif as compared to that seen in other kinase compl  ...[more]

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