1h4l: Difference between revisions
New page: left|200px<br /> <applet load="1h4l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h4l, resolution 2.65Å" /> '''STRUCTURE AND REGUL... |
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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" | ||
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caption="1h4l, resolution 2.65Å" /> | caption="1h4l, resolution 2.65Å" /> | ||
'''STRUCTURE AND REGULATION OF THE CDK5-P25(NCK5A) COMPLEX'''<br /> | '''STRUCTURE AND REGULATION OF THE CDK5-P25(NCK5A) COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
CDK5 plays an indispensable role in the central nervous system, and its | 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== | ==Disease== | ||
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==About this Structure== | ==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:// | 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== | ==Reference== | ||
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[[Category: Peng, J.]] | [[Category: Peng, J.]] | ||
[[Category: Tarricone, C.]] | [[Category: Tarricone, C.]] | ||
[[Category: Tsai, L | [[Category: Tsai, L H.]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
[[Category: cdk5]] | [[Category: cdk5]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:57:22 2008'' | ||
Revision as of 10:57, 21 February 2008
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STRUCTURE AND REGULATION OF THE CDK5-P25(NCK5A) COMPLEX
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.
Disease
Known diseases associated with this structure: Microcephaly, primary autosomal recessive, 3 OMIM:[608201]
About this Structure
1H4L is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and regulation of the CDK5-p25(nck5a) complex., Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A, Mol Cell. 2001 Sep;8(3):657-69. PMID:11583627
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