2BFX

Mechanism of Aurora-B activation by INCENP and inhibition by Hesperadin.

Summary for 2BFX

• Entry DOI: 10.2210/pdb2bfx/pdb
• Related: 2BFY
• Descriptor: AURORA KINASE B-A, INNER CENTROMERE PROTEIN A (3 entities in total)
• Functional Keywords: transferase, kinase, mitosis, inhibition, transferase complex
• Biological source: XENOPUS LAEVIS (AFRICAN CLAWED FROG); More
• Cellular location: Nucleus: Q6DE08; Chromosome, centromere: O13024
• Total number of polymer chains: 4
• Total formula weight: 77029.02

Authors

Sessa, F.,Mapelli, M.,Ciferri, C.,Tarricone, C.,Areces, L.B.,Schneider, T.R.,Stukenberg, P.T.,Musacchio, A. (deposition date: 2004-12-15, release date: 2005-05-03, Last modification date: 2024-11-13)

Primary citation

Sessa, F.,Mapelli, M.,Ciferri, C.,Tarricone, C.,Areces, L.B.,Schneider, T.R.,Stukenberg, P.T.,Musacchio, A.
Mechanism of Aurora B Activation by Incenp and Inhibition by Hesperadin
Mol.Cell, 18:379-, 2005

PubMed Abstract: Aurora family serine/threonine kinases control mitotic progression, and their deregulation is implicated in tumorigenesis. Aurora A and Aurora B, the best-characterized members of mammalian Aurora kinases, are approximately 60% identical but bind to unrelated activating subunits. The structure of the complex of Aurora A with the TPX2 activator has been reported previously. Here, we report the crystal structure of Aurora B in complex with the IN-box segment of the inner centromere protein (INCENP) activator and with the small molecule inhibitor Hesperadin. The Aurora B:INCENP complex is remarkably different from the Aurora A:TPX2 complex. INCENP forms a crown around the small lobe of Aurora B and induces the active conformation of the T loop allosterically. The structure represents an intermediate state of activation of Aurora B in which the Aurora B C-terminal segment stabilizes an open conformation of the catalytic cleft, and a critical ion pair in the kinase active site is impaired. Phosphorylation of two serines in the carboxyl terminus of INCENP generates the fully active kinase.

PubMed: 15866179
DOI: 10.1016/J.MOLCEL.2005.03.031

Experimental method

X-RAY DIFFRACTION (1.8 Å)