1ckp: Difference between revisions
New page: left|200px<br /> <applet load="1ckp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ckp, resolution 2.05Å" /> '''HUMAN CYCLIN DEPEND... |
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[[Image:1ckp.gif|left|200px]]<br /> | [[Image:1ckp.gif|left|200px]]<br /><applet load="1ckp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1ckp" size=" | |||
caption="1ckp, resolution 2.05Å" /> | caption="1ckp, resolution 2.05Å" /> | ||
'''HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR PURVALANOL B'''<br /> | '''HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR PURVALANOL B'''<br /> | ||
==Overview== | ==Overview== | ||
Selective protein kinase inhibitors were developed on the basis of the | Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). By iterating chemical library synthesis and biological screening, potent inhibitors of the human CDK2-cyclin A kinase complex and of Saccharomyces cerevisiae Cdc28p were identified. The structural basis for the binding affinity and selectivity was determined by analysis of a three-dimensional crystal structure of a CDK2-inhibitor complex. The cellular effects of these compounds were characterized in mammalian cells and yeast. In the latter case the effects were characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays. Purine libraries could provide useful tools for analyzing a variety of signaling and regulatory pathways and may lead to the development of new therapeutics. | ||
==About this Structure== | ==About this Structure== | ||
1CKP 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 PVB and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | 1CKP 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=PVB:'>PVB</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1CKP 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: Gray, N | [[Category: Gray, N S.]] | ||
[[Category: Kim, S | [[Category: Kim, S H.]] | ||
[[Category: Schultz, P | [[Category: Schultz, P G.]] | ||
[[Category: Thunnissen, A | [[Category: Thunnissen, A M.W H.]] | ||
[[Category: EDO]] | [[Category: EDO]] | ||
[[Category: PVB]] | [[Category: PVB]] | ||
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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 12:07:03 2008'' | ||
Revision as of 13:07, 21 February 2008
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HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR PURVALANOL B
OverviewOverview
Selective protein kinase inhibitors were developed on the basis of the unexpected binding mode of 2,6,9-trisubstituted purines to the adenosine triphosphate-binding site of the human cyclin-dependent kinase 2 (CDK2). By iterating chemical library synthesis and biological screening, potent inhibitors of the human CDK2-cyclin A kinase complex and of Saccharomyces cerevisiae Cdc28p were identified. The structural basis for the binding affinity and selectivity was determined by analysis of a three-dimensional crystal structure of a CDK2-inhibitor complex. The cellular effects of these compounds were characterized in mammalian cells and yeast. In the latter case the effects were characterized on a genome-wide scale by monitoring changes in messenger RNA levels in treated cells with high-density oligonucleotide probe arrays. Purine libraries could provide useful tools for analyzing a variety of signaling and regulatory pathways and may lead to the development of new therapeutics.
About this StructureAbout this Structure
1CKP is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
ReferenceReference
Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors., Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, Morgan DO, Barnes G, LeClerc S, Meijer L, Kim SH, Lockhart DJ, Schultz PG, Science. 1998 Jul 24;281(5376):533-8. PMID:9677190
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