1unh
From Proteopedia
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| - | [[Image:1unh.gif|left|200px]]<br /><applet load="1unh" size=" | + | [[Image:1unh.gif|left|200px]]<br /><applet load="1unh" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1unh, resolution 2.35Å" /> | caption="1unh, resolution 2.35Å" /> | ||
'''STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.'''<br /> | '''STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UNH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with IXM as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Ixm Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http:// | + | 1UNH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=IXM:'>IXM</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Ixm+Binding+Site+For+Chain+B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UNH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: neurodegenerative diseases]] | [[Category: neurodegenerative diseases]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:03:04 2008'' |
Revision as of 08:03, 3 February 2008
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STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.
Contents |
Overview
The cyclin-dependent kinases (CDK) CDK1, CDK2, CDK4, and CDK6 are, serine/threonine protein kinases targeted in cancer therapy due to their, role in cell cycle progression. The postmitotic CDK5 is involved in, biological pathways important for neuronal migration and differentiation., CDK5 represents an attractive pharmacological target as its deregulation, is implicated in various neurodegenerative diseases such as Alzheimer's, Parkinson's, and Niemann-Pick type C diseases, ischemia, and amyotrophic, lateral sclerosis. We have generated an improved crystal form of CDK5 in, complex with p25, a segment of the p35 neuronal activator. The crystals, were used to solve the structure of CDK5/p25 with (R)-roscovitine and, aloisine at a resolution of 2.2 and 2.3 A, respectively. The structure of, CDK5/p25/roscovitine provides a rationale for the preference of CDK5 for, the R over the S stereoisomer. Furthermore, roscovitine stabilized an, unusual collapsed conformation of the glycine-rich loop, an important site, of CDK regulation, and we report an investigation of the effects of, glycine-rich loop phosphorylation on roscovitine binding. The CDK5/p25, crystals represent a valuable new tool for the identification and, optimization of selective CDK inhibitors.
Disease
Known diseases associated with this structure: Microcephaly, primary autosomal recessive, 3 OMIM:[608201]
About this Structure
1UNH is a Protein complex structure of sequences from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Mechanism of CDK5/p25 binding by CDK inhibitors., Mapelli M, Massimiliano L, Crovace C, Seeliger MA, Tsai LH, Meijer L, Musacchio A, J Med Chem. 2005 Feb 10;48(3):671-9. PMID:15689152
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