1ykr
From Proteopedia
(New page: 200px<br /> <applet load="1ykr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ykr, resolution 1.8Å" /> '''Crystal structure of...) |
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- | [[Image:1ykr.gif|left|200px]]<br /> | + | [[Image:1ykr.gif|left|200px]]<br /><applet load="1ykr" size="350" color="white" frame="true" align="right" spinBox="true" |
- | <applet load="1ykr" size=" | + | |
caption="1ykr, resolution 1.8Å" /> | caption="1ykr, resolution 1.8Å" /> | ||
'''Crystal structure of cdk2 with an aminoimidazo pyridine inhibitor'''<br /> | '''Crystal structure of cdk2 with an aminoimidazo pyridine inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
- | Structure-based design approach was successfully used to guide the | + | Structure-based design approach was successfully used to guide the evolution of imidazopyridine scaffold yielding new structural class of highly selective inhibitors of cyclin dependent kinases that were able to form a new interaction with an identified residue of the protein, Lys89. Compounds from this series have shown no detectable effect when tested against a representative set of other serine/threonine kinases such as GSK3beta, CAMKII, PKA, PKC-alpha,beta,epsilon,gamma. Compound 2i inhibits proliferation in HCT 116 cells in tissue culture. Synthesis, co-crystal structure of CDK2 in complex with compound 2i, and preliminary SAR study are disclosed. |
==About this Structure== | ==About this Structure== | ||
- | 1YKR 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 628 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:// | + | 1YKR 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=628:'>628</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=1YKR 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: Brooks, H | + | [[Category: Brooks, H B.]] |
[[Category: Hamdouchi, C.]] | [[Category: Hamdouchi, C.]] | ||
[[Category: Jaramillo, C.]] | [[Category: Jaramillo, C.]] | ||
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[[Category: cell cycle division protein kinase 2]] | [[Category: cell cycle division protein kinase 2]] | ||
- | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:06:19 2008'' |
Revision as of 14:06, 21 February 2008
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Crystal structure of cdk2 with an aminoimidazo pyridine inhibitor
Overview
Structure-based design approach was successfully used to guide the evolution of imidazopyridine scaffold yielding new structural class of highly selective inhibitors of cyclin dependent kinases that were able to form a new interaction with an identified residue of the protein, Lys89. Compounds from this series have shown no detectable effect when tested against a representative set of other serine/threonine kinases such as GSK3beta, CAMKII, PKA, PKC-alpha,beta,epsilon,gamma. Compound 2i inhibits proliferation in HCT 116 cells in tissue culture. Synthesis, co-crystal structure of CDK2 in complex with compound 2i, and preliminary SAR study are disclosed.
About this Structure
1YKR 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 of a new class of highly selective aminoimidazo[1,2-a]pyridine-based inhibitors of cyclin dependent kinases., Hamdouchi C, Zhong B, Mendoza J, Collins E, Jaramillo C, De Diego JE, Robertson D, Spencer CD, Anderson BD, Watkins SA, Zhang F, Brooks HB, Bioorg Med Chem Lett. 2005 Apr 1;15(7):1943-7. PMID:15780638
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