2a0c: Difference between revisions
New page: left|200px<br /> <applet load="2a0c" size="450" color="white" frame="true" align="right" spinBox="true" caption="2a0c, resolution 1.95Å" /> '''Human CDK2 in compl... |
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[[Image:2a0c.gif|left|200px]]<br /> | [[Image:2a0c.gif|left|200px]]<br /><applet load="2a0c" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2a0c, resolution 1.95Å" /> | caption="2a0c, resolution 1.95Å" /> | ||
'''Human CDK2 in complex with olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor'''<br /> | '''Human CDK2 in complex with olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
The study describes the protein kinase selectivity profile, as well as the | The study describes the protein kinase selectivity profile, as well as the binding mode of olomoucine II in the catalytic cleft of CDK2, as determined from cocrystal analysis. Apart from the main cell cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7 and CDK9, with important functions in the regulation of RNA transcription. In vitro anticancer activity of the inhibitor in a panel of tumor cell lines shows a wide potency range with a slight preference for cells harboring a wild-type p53 gene. Cell-based assays confirmed activation of p53 protein levels and events leading to accumulation of p21(WAF1). Additionally, in olomoucine II-treated cells, Mdm2 was found to form a complex with the ribosomal protein L11, which inhibits Mdm2 ubiquitin ligase function. We conclude that perturbations in RNA synthesis may lead to activation of p53 and that this contributes to the antiproliferative potency of cyclindependent kinase inhibitors. | ||
==About this Structure== | ==About this Structure== | ||
2A0C 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 CK9 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | 2A0C 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=CK9:'>CK9</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2A0C OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Fischer, P | [[Category: Fischer, P M.]] | ||
[[Category: Havlicek, L.]] | [[Category: Havlicek, L.]] | ||
[[Category: Krystof, V.]] | [[Category: Krystof, V.]] | ||
[[Category: McNae, I | [[Category: McNae, I W.]] | ||
[[Category: Muller, P.]] | [[Category: Muller, P.]] | ||
[[Category: Orsag, M.]] | [[Category: Orsag, M.]] | ||
[[Category: Strnad, M.]] | [[Category: Strnad, M.]] | ||
[[Category: Vojtesek, B.]] | [[Category: Vojtesek, B.]] | ||
[[Category: Walkinshaw, M | [[Category: Walkinshaw, M D.]] | ||
[[Category: CK9]] | [[Category: CK9]] | ||
[[Category: 3d-structure]] | [[Category: 3d-structure]] | ||
| Line 36: | Line 35: | ||
[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:22:26 2008'' | ||
Revision as of 17:22, 21 February 2008
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Human CDK2 in complex with olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor
OverviewOverview
The study describes the protein kinase selectivity profile, as well as the binding mode of olomoucine II in the catalytic cleft of CDK2, as determined from cocrystal analysis. Apart from the main cell cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7 and CDK9, with important functions in the regulation of RNA transcription. In vitro anticancer activity of the inhibitor in a panel of tumor cell lines shows a wide potency range with a slight preference for cells harboring a wild-type p53 gene. Cell-based assays confirmed activation of p53 protein levels and events leading to accumulation of p21(WAF1). Additionally, in olomoucine II-treated cells, Mdm2 was found to form a complex with the ribosomal protein L11, which inhibits Mdm2 ubiquitin ligase function. We conclude that perturbations in RNA synthesis may lead to activation of p53 and that this contributes to the antiproliferative potency of cyclindependent kinase inhibitors.
About this StructureAbout this Structure
2A0C is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
ReferenceReference
Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor., Krystof V, McNae IW, Walkinshaw MD, Fischer PM, Muller P, Vojtesek B, Orsag M, Havlicek L, Strnad M, Cell Mol Life Sci. 2005 Aug;62(15):1763-71. PMID:16003486
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Non-specific serine/threonine protein kinase
- Single protein
- Fischer, P M.
- Havlicek, L.
- Krystof, V.
- McNae, I W.
- Muller, P.
- Orsag, M.
- Strnad, M.
- Vojtesek, B.
- Walkinshaw, M D.
- CK9
- 3d-structure
- Atp-binding
- Cell cycle
- Cell division
- Inhibition
- Mitosis
- Phosphorylation
- Protein kinase
- Serine/threonine-protein kinase
- Transferase