4AF3

Human Aurora B Kinase in complex with INCENP and VX-680

Summary for 4AF3

• Entry DOI: 10.2210/pdb4af3/pdb
• Descriptor: AURORA KINASE B, INNER CENTROMERE PROTEIN, CYCLOPROPANECARBOXYLIC ACID {4-[4-(4-METHYL-PIPERAZIN-1-YL)-6-(5-METHYL-2H-PYRAZOL-3-YLAMINO)-PYRIMIDIN-2-YLSULFANYL]-PHENYL}-AMIDE, ... (4 entities in total)
• Functional Keywords: transferase-inhibitor complex, aurkb, transferase/inhibitor
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: Q96GD4 Q9NQS7
• Total number of polymer chains: 2
• Total formula weight: 42400.17

Authors

Elkins, J.M.,Vollmar, M.,Wang, J.,Picaud, S.,Arrowsmith, C.H.,Edwards, A.,Bountra, C.,von Delft, F.,Knapp, S. (deposition date: 2012-01-16, release date: 2012-04-11, Last modification date: 2023-12-20)

Primary citation

Elkins, J.M.,Santaguida, S.,Musacchio, A.,Knapp, S.
Crystal Structure of Human Aurora B in Complex with Incenp and Vx-680.
J.Med.Chem., 55:7841-, 2012

PubMed 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.

PubMed: 22920039
DOI: 10.1021/JM3008954

Experimental method

X-RAY DIFFRACTION (2.75 Å)