1pmv
From Proteopedia
(New page: 200px<br /> <applet load="1pmv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pmv, resolution 2.5Å" /> '''The structure of JNK...) |
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| - | [[Image:1pmv.gif|left|200px]]<br /> | + | [[Image:1pmv.gif|left|200px]]<br /><applet load="1pmv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1pmv" size=" | + | |
caption="1pmv, resolution 2.5Å" /> | caption="1pmv, resolution 2.5Å" /> | ||
'''The structure of JNK3 in complex with a dihydroanthrapyrazole inhibitor'''<br /> | '''The structure of JNK3 in complex with a dihydroanthrapyrazole inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The c-Jun terminal kinases (JNKs) are members of the mitogen-activated | + | The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1PMV 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 537 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1PMV 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=537:'>537</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PMV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Becker, J | + | [[Category: Becker, J W.]] |
[[Category: Lisnock, J.]] | [[Category: Lisnock, J.]] | ||
| - | [[Category: LoGrasso, P | + | [[Category: LoGrasso, P V.]] |
| - | [[Category: Patel, S | + | [[Category: Patel, S B.]] |
[[Category: Scapin, G.]] | [[Category: Scapin, G.]] | ||
[[Category: 537]] | [[Category: 537]] | ||
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[[Category: selectivity]] | [[Category: selectivity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:30:23 2008'' |
Revision as of 12:30, 21 February 2008
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The structure of JNK3 in complex with a dihydroanthrapyrazole inhibitor
Contents |
Overview
The c-Jun terminal kinases (JNKs) are members of the mitogen-activated protein (MAP) kinase family and regulate signal transduction in response to environmental stress. Activation of JNK3, a neuronal-specific isoform, has been associated with neurological damage, and as such, JNK3 may represent an attractive target for the treatment of neurological disorders. The MAP kinases share between 50% and 80% sequence identity. In order to obtain efficacious and safe compounds, it is necessary to address the issues of potency and selectivity. We report here four crystal structures of JNK3 in complex with three different classes of inhibitors. These structures provide a clear picture of the interactions that each class of compound made with the kinase. Knowledge of the atomic interactions involved in these diverse binding modes provides a platform for structure-guided modification of these compounds, or the de novo design of novel inhibitors that could satisfy the need for potency and selectivity.
Disease
Known diseases associated with this structure: Epileptic encephalopathy, Lennox-Gastaut type OMIM:[602897]
About this Structure
1PMV is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity., Scapin G, Patel SB, Lisnock J, Becker JW, LoGrasso PV, Chem Biol. 2003 Aug;10(8):705-12. PMID:12954329
Page seeded by OCA on Thu Feb 21 14:30:23 2008
Categories: Homo sapiens | Single protein | Becker, J W. | Lisnock, J. | LoGrasso, P V. | Patel, S B. | Scapin, G. | 537 | Apoptosis | Inhibition | Map kinase | Selectivity
