2bfx
From Proteopedia
(New page: 200px<br /><applet load="2bfx" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bfx, resolution 1.80Å" /> '''MECHANISM OF AURORA-...) |
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| - | [[Image:2bfx.gif|left|200px]]<br /><applet load="2bfx" size=" | + | [[Image:2bfx.gif|left|200px]]<br /><applet load="2bfx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2bfx, resolution 1.80Å" /> | caption="2bfx, resolution 1.80Å" /> | ||
'''MECHANISM OF AURORA-B ACTIVATION BY INCENP AND INHIBITION BY HESPERIDIN.'''<br /> | '''MECHANISM OF AURORA-B ACTIVATION BY INCENP AND INHIBITION BY HESPERIDIN.'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Aurora family serine/threonine kinases control mitotic progression, and | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2BFX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http:// | + | 2BFX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BFX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Xenopus laevis]] | [[Category: Xenopus laevis]] | ||
| - | [[Category: Areces, L | + | [[Category: Areces, L B.]] |
[[Category: Ciferri, C.]] | [[Category: Ciferri, C.]] | ||
[[Category: Mapelli, M.]] | [[Category: Mapelli, M.]] | ||
[[Category: Musacchio, A.]] | [[Category: Musacchio, A.]] | ||
| - | [[Category: Schneider, T | + | [[Category: Schneider, T R.]] |
[[Category: Sessa, F.]] | [[Category: Sessa, F.]] | ||
| - | [[Category: Stukenberg, P | + | [[Category: Stukenberg, P T.]] |
[[Category: Tarricone, C.]] | [[Category: Tarricone, C.]] | ||
[[Category: inhibition]] | [[Category: inhibition]] | ||
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[[Category: transferase complex]] | [[Category: transferase complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:37:24 2008'' |
Revision as of 14:37, 21 February 2008
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MECHANISM OF AURORA-B ACTIVATION BY INCENP AND INHIBITION BY HESPERIDIN.
Overview
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.
About this Structure
2BFX is a Protein complex structure of sequences from Xenopus laevis. Full crystallographic information is available from OCA.
Reference
Mechanism of Aurora B activation by INCENP and inhibition by hesperadin., Sessa F, Mapelli M, Ciferri C, Tarricone C, Areces LB, Schneider TR, Stukenberg PT, Musacchio A, Mol Cell. 2005 Apr 29;18(3):379-91. PMID:15866179
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