1jvp
From Proteopedia
(New page: 200px<br /> <applet load="1jvp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jvp, resolution 1.53Å" /> '''Crystal structure o...) |
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| - | [[Image:1jvp.gif|left|200px]]<br /> | + | [[Image:1jvp.gif|left|200px]]<br /><applet load="1jvp" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1jvp" size=" | + | |
caption="1jvp, resolution 1.53Å" /> | caption="1jvp, resolution 1.53Å" /> | ||
'''Crystal structure of human CDK2 (unphosphorylated) in complex with PKF049-365'''<br /> | '''Crystal structure of human CDK2 (unphosphorylated) in complex with PKF049-365'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP | + | A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP binding site of cyclin dependent kinase 2 (CDK2) on the basis of crystallographic information. A search of the compound collection of Novartis using this scaffold as substructure query led to the identification of PKF049-365 as a representative of a new class of inhibitors of the cell cycle kinases CDK1/2. The three-dimensional structure of CDK2 in complex with PKF049-365 was subsequently determined by protein crystallography and refined to 1.53 A resolution. The X-ray analysis confirmed the binding mode expected from the design hypothesis. In addition, it revealed an alternative binding orientation involving a second tautomeric form of the inhibitor that was not envisaged during the design stage. |
==About this Structure== | ==About this Structure== | ||
| - | 1JVP 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 LIG 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:// | + | 1JVP 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=LIG:'>LIG</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=1JVP 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: Rondeau, J | + | [[Category: Rondeau, J M.]] |
[[Category: LIG]] | [[Category: LIG]] | ||
[[Category: cell cycle]] | [[Category: cell cycle]] | ||
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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 13:27:16 2008'' |
Revision as of 11:27, 21 February 2008
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Crystal structure of human CDK2 (unphosphorylated) in complex with PKF049-365
Overview
A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP binding site of cyclin dependent kinase 2 (CDK2) on the basis of crystallographic information. A search of the compound collection of Novartis using this scaffold as substructure query led to the identification of PKF049-365 as a representative of a new class of inhibitors of the cell cycle kinases CDK1/2. The three-dimensional structure of CDK2 in complex with PKF049-365 was subsequently determined by protein crystallography and refined to 1.53 A resolution. The X-ray analysis confirmed the binding mode expected from the design hypothesis. In addition, it revealed an alternative binding orientation involving a second tautomeric form of the inhibitor that was not envisaged during the design stage.
About this Structure
1JVP 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.
Reference
Structure-based design and protein X-ray analysis of a protein kinase inhibitor., Furet P, Meyer T, Strauss A, Raccuglia S, Rondeau JM, Bioorg Med Chem Lett. 2002 Jan 21;12(2):221-4. PMID:11755359
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