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| {{STRUCTURE_1dm2| PDB=1dm2 | SCENE= }} | | {{STRUCTURE_1dm2| PDB=1dm2 | SCENE= }} |
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| '''HUMAN CYCLIN-DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR HYMENIALDISINE'''
| | ===HUMAN CYCLIN-DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR HYMENIALDISINE=== |
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| ==Overview==
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| BACKGROUND: Over 2000 protein kinases regulate cellular functions. Screening for inhibitors of some of these kinases has already yielded some potent and selective compounds with promising potential for the treatment of human diseases. RESULTS: The marine sponge constituent hymenialdisine is a potent inhibitor of cyclin-dependent kinases, glycogen synthase kinase-3beta and casein kinase 1. Hymenialdisine competes with ATP for binding to these kinases. A CDK2-hymenialdisine complex crystal structure shows that three hydrogen bonds link hymenialdisine to the Glu81 and Leu83 residues of CDK2, as observed with other inhibitors. Hymenialdisine inhibits CDK5/p35 in vivo as demonstrated by the lack of phosphorylation/down-regulation of Pak1 kinase in E18 rat cortical neurons, and also inhibits GSK-3 in vivo as shown by the inhibition of MAP-1B phosphorylation. Hymenialdisine also blocks the in vivo phosphorylation of the microtubule-binding protein tau at sites that are hyperphosphorylated by GSK-3 and CDK5/p35 in Alzheimer's disease (cross-reacting with Alzheimer's-specific AT100 antibodies). CONCLUSIONS: The natural product hymenialdisine is a new kinase inhibitor with promising potential applications for treating neurodegenerative disorders.
| | The line below this paragraph, {{ABSTRACT_PUBMED_10662688}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 10662688 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_10662688}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Phosphorylation]] | | [[Category: Phosphorylation]] |
| [[Category: Protein kinase]] | | [[Category: Protein kinase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:00:28 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 23:16:36 2008'' |
