1unh
From Proteopedia
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| - | [[Image:1unh.gif|left|200px]] | + | [[Image:1unh.gif|left|200px]] |
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| - | '''STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.''' | + | {{Structure |
| + | |PDB= 1unh |SIZE=350|CAPTION= <scene name='initialview01'>1unh</scene>, resolution 2.35Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Ixm+Binding+Site+For+Chain+B'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=IXM:(Z)-1H,1'H-[2,3']BIINDOLYLIDENE-3,2'-DIONE-3-OXIME'>IXM</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UNH is a [ | + | 1UNH is a [[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=1UNH OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15689152 15689152] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: cyclin-dependent kinase]] | [[Category: cyclin-dependent kinase]] | ||
[[Category: indirubin]] | [[Category: indirubin]] | ||
| - | [[Category: | + | [[Category: inhibitor]] |
| - | [[Category: neurodegenerative | + | [[Category: neurodegenerative disease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:34:21 2008'' |
Revision as of 12:34, 20 March 2008
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| , resolution 2.35Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Thu Mar 20 14:34:21 2008
