1dm2
From Proteopedia
(New page: 200px<br /> <applet load="1dm2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dm2, resolution 2.1Å" /> '''HUMAN CYCLIN-DEPENDE...) |
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| - | [[Image:1dm2.gif|left|200px]]<br /> | + | [[Image:1dm2.gif|left|200px]]<br /><applet load="1dm2" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dm2" size=" | + | |
caption="1dm2, resolution 2.1Å" /> | caption="1dm2, resolution 2.1Å" /> | ||
'''HUMAN CYCLIN-DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR HYMENIALDISINE'''<br /> | '''HUMAN CYCLIN-DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR HYMENIALDISINE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Over 2000 protein kinases regulate cellular functions. | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1DM2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HMD and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1DM2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HMD:'>HMD</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DM2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Kim, S | + | [[Category: Kim, S H.]] |
| - | [[Category: Thunnissen, A | + | [[Category: Thunnissen, A M.]] |
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: HMD]] | [[Category: HMD]] | ||
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[[Category: protein kinase]] | [[Category: protein kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:17:57 2008'' |
Revision as of 10:18, 21 February 2008
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HUMAN CYCLIN-DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR HYMENIALDISINE
Overview
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.
About this Structure
1DM2 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent., Meijer L, Thunnissen AM, White AW, Garnier M, Nikolic M, Tsai LH, Walter J, Cleverley KE, Salinas PC, Wu YZ, Biernat J, Mandelkow EM, Kim SH, Pettit GR, Chem Biol. 2000 Jan;7(1):51-63. PMID:10662688
Page seeded by OCA on Thu Feb 21 12:17:57 2008
Categories: Homo sapiens | Single protein | Kim, S H. | Thunnissen, A M. | EDO | HMD | Cell cycle | Cell division | Inhibition | Mitosis | Phosphorylation | Protein kinase
