1h4l: Difference between revisions

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[[Image:1h4l.gif|left|200px]]<br />

[[Image:1h4l.gif|left|200px]]<br /><applet load="1h4l" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1h4l" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1h4l, resolution 2.65Å" />

'''STRUCTURE AND REGULATION OF THE CDK5-P25(NCK5A) COMPLEX'''<br />

==Overview==

CDK5 plays an indispensable role in the central nervous system, and its, deregulation is involved in neurodegeneration. We report the crystal, structure of a complex between CDK5 and p25, a fragment of the p35, activator. Despite its partial structural similarity with the cyclins, p25, displays an unprecedented mechanism for the regulation of a, cyclin-dependent kinase. p25 tethers the unphosphorylated T loop of CDK5, in the active conformation. Residue Ser159, equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35 interaction. Its, substitution with threonine prevents p35 binding, while the presence of, alanine affects neither binding nor kinase activity. Finally, we provide, evidence that the CDK5-p25 complex employs a distinct mechanism from the, phospho-CDK2-cyclin A complex to establish substrate specificity.

CDK5 plays an indispensable role in the central nervous system, and its deregulation is involved in neurodegeneration. We report the crystal structure of a complex between CDK5 and p25, a fragment of the p35 activator. Despite its partial structural similarity with the cyclins, p25 displays an unprecedented mechanism for the regulation of a cyclin-dependent kinase. p25 tethers the unphosphorylated T loop of CDK5 in the active conformation. Residue Ser159, equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35 interaction. Its substitution with threonine prevents p35 binding, while the presence of alanine affects neither binding nor kinase activity. Finally, we provide evidence that the CDK5-p25 complex employs a distinct mechanism from the phospho-CDK2-cyclin A complex to establish substrate specificity.

==Disease==

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==About this Structure==

1H4L is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1H4L OCA].

1H4L is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H4L OCA].

==Reference==

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[[Category: Peng, J.]]

[[Category: Tarricone, C.]]

[[Category: Tsai, L.H.]]

[[Category: Tsai, L H.]]

[[Category: atp-binding]]

[[Category: cdk5]]

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[[Category: transferase]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov~~ 12 17:12:~~45 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:57:22 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1h4l.gif|left|200px]]<br />
+[[Image:1h4l.gif|left|200px]]<br /><applet load="1h4l" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1h4l" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1h4l, resolution 2.65&Aring;" />
 '''STRUCTURE AND REGULATION OF THE CDK5-P25(NCK5A) COMPLEX'''<br />
 ==Overview==
-CDK5 plays an indispensable role in the central nervous system, and its, deregulation is involved in neurodegeneration. We report the crystal, structure of a complex between CDK5 and p25, a fragment of the p35, activator. Despite its partial structural similarity with the cyclins, p25, displays an unprecedented mechanism for the regulation of a, cyclin-dependent kinase. p25 tethers the unphosphorylated T loop of CDK5, in the active conformation. Residue Ser159, equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35 interaction. Its, substitution with threonine prevents p35 binding, while the presence of, alanine affects neither binding nor kinase activity. Finally, we provide, evidence that the CDK5-p25 complex employs a distinct mechanism from the, phospho-CDK2-cyclin A complex to establish substrate specificity.
+CDK5 plays an indispensable role in the central nervous system, and its deregulation is involved in neurodegeneration. We report the crystal structure of a complex between CDK5 and p25, a fragment of the p35 activator. Despite its partial structural similarity with the cyclins, p25 displays an unprecedented mechanism for the regulation of a cyclin-dependent kinase. p25 tethers the unphosphorylated T loop of CDK5 in the active conformation. Residue Ser159, equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35 interaction. Its substitution with threonine prevents p35 binding, while the presence of alanine affects neither binding nor kinase activity. Finally, we provide evidence that the CDK5-p25 complex employs a distinct mechanism from the phospho-CDK2-cyclin A complex to establish substrate specificity.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-H4L is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H4L OCA].
+H4L is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H4L OCA].
 ==Reference==
@@ Line 22: / Line 21: @@
 [[Category: Peng, J.]]
 [[Category: Tarricone, C.]]
-[[Category: Tsai, L.H.]]
+[[Category: Tsai, L H.]]
 [[Category: atp-binding]]
 [[Category: cdk5]]
@@ Line 34: / Line 33: @@
 [[Category: transferase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:12:45 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:57:22 2008''