2bfx: Difference between revisions

Line 1:

[[Image:2bfx.gif|left|200px]]<br /><applet load="2bfx" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:2bfx.gif|left|200px]]<br /><applet load="2bfx" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2bfx, resolution 1.80Å" />

'''MECHANISM OF AURORA-B ACTIVATION BY INCENP AND INHIBITION BY HESPERIDIN.'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2BFX OCA].

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==

Line 13:

[[Category: Protein complex]]

[[Category: Xenopus laevis]]

[[Category: Areces, L.B.]]

[[Category: Areces, L B.]]

[[Category: Ciferri, C.]]

[[Category: Mapelli, M.]]

[[Category: Musacchio, A.]]

[[Category: Schneider, T.R.]]

[[Category: Schneider, T R.]]

[[Category: Sessa, F.]]

[[Category: Stukenberg, P.T.]]

[[Category: Stukenberg, P T.]]

[[Category: Tarricone, C.]]

[[Category: inhibition]]

Line 26:

[[Category: transferase complex]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 08:46:~~38 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:37:24 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:2bfx.gif|left|200px]]<br /><applet load="2bfx" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2bfx.gif|left|200px]]<br /><applet load="2bfx" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2bfx, resolution 1.80&Aring;" />
 '''MECHANISM OF AURORA-B ACTIVATION BY INCENP AND INHIBITION BY HESPERIDIN.'''<br />
 ==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.
+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==
-BFX 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BFX OCA].
+BFX 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==
@@ Line 13: / Line 13: @@
 [[Category: Protein complex]]
 [[Category: Xenopus laevis]]
-[[Category: Areces, L.B.]]
+[[Category: Areces, L B.]]
 [[Category: Ciferri, C.]]
 [[Category: Mapelli, M.]]
 [[Category: Musacchio, A.]]
-[[Category: Schneider, T.R.]]
+[[Category: Schneider, T R.]]
 [[Category: Sessa, F.]]
-[[Category: Stukenberg, P.T.]]
+[[Category: Stukenberg, P T.]]
 [[Category: Tarricone, C.]]
 [[Category: inhibition]]
@@ Line 26: / Line 26: @@
 [[Category: transferase complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:46:38 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:37:24 2008''