Crystal Structure of Human Aurora B in Complex with INCENP and VX-680
Open Access
- 4 September 2012
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 55 (17), 7841-7848
- https://doi.org/10.1021/jm3008954
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.Keywords
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