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PDBsum entry 2bfy
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References listed in PDB file
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Key reference
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Title
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Mechanism of aurora b activation by incenp and inhibition by hesperadin.
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Authors
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F.Sessa,
M.Mapelli,
C.Ciferri,
C.Tarricone,
L.B.Areces,
T.R.Schneider,
P.T.Stukenberg,
A.Musacchio.
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Ref.
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Mol Cell, 2005,
18,
379-391.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 3.
Figure 3. Details of the Aurora B:IN-box Interaction
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Figure 5.
Figure 5. Activation Mechanism of Aurora B
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The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2005,
18,
379-391)
copyright 2005.
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