1pxl
From Proteopedia
(New page: 200px<br /> <applet load="1pxl" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pxl, resolution 2.50Å" /> '''HUMAN CYCLIN DEPEND...) |
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| - | [[Image:1pxl.gif|left|200px]]<br /> | + | [[Image:1pxl.gif|left|200px]]<br /><applet load="1pxl" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1pxl" size=" | + | |
caption="1pxl, resolution 2.50Å" /> | caption="1pxl, resolution 2.50Å" /> | ||
'''HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR [4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-(4-trifluoromethyl-phenyl)-amine'''<br /> | '''HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR [4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-(4-trifluoromethyl-phenyl)-amine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A family of 4-heteroaryl-2-amino-pyrimidine CDK2 inhibitor lead compounds | + | A family of 4-heteroaryl-2-amino-pyrimidine CDK2 inhibitor lead compounds was discovered with the new database-mining program LIDAEUS through in silico screening. Four compounds with IC(50) values ranging from 17 to 0.9 microM were selected for X-ray crystal analysis. Two distinct binding modes are observed, one of which resembles the hydrogen bonding pattern of bound ATP. In the second binding mode, the ligands trigger a conformational change in the activation T loop by inducing movement of Lys(33) and Asp(145) side chains. The family of molecules discovered provides an excellent starting point for the design and synthesis of tight binding inhibitors, which may lead to a new class of antiproliferative drugs. |
==About this Structure== | ==About this Structure== | ||
| - | 1PXL 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 CK4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1PXL 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=CK4:'>CK4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PXL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fischer, P | + | [[Category: Fischer, P M.]] |
[[Category: Kontopidis, G.]] | [[Category: Kontopidis, G.]] | ||
| - | [[Category: Lane, D | + | [[Category: Lane, D P.]] |
[[Category: Marriage, H.]] | [[Category: Marriage, H.]] | ||
| - | [[Category: McClue, S | + | [[Category: McClue, S J.]] |
[[Category: McInnes, C.]] | [[Category: McInnes, C.]] | ||
[[Category: McNae, I.]] | [[Category: McNae, I.]] | ||
| - | [[Category: Stewart, K | + | [[Category: Stewart, K J.]] |
[[Category: Taylor, P.]] | [[Category: Taylor, P.]] | ||
| - | [[Category: Walkinshaw, M | + | [[Category: Walkinshaw, M D.]] |
[[Category: Wang, S.]] | [[Category: Wang, S.]] | ||
| - | [[Category: Wu, S | + | [[Category: Wu, S Y.]] |
| - | [[Category: Zheleva, D | + | [[Category: Zheleva, D I.]] |
[[Category: CK4]] | [[Category: CK4]] | ||
[[Category: 3d-structure.]] | [[Category: 3d-structure.]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:33:34 2008'' |
Revision as of 12:33, 21 February 2008
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HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR [4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-(4-trifluoromethyl-phenyl)-amine
Overview
A family of 4-heteroaryl-2-amino-pyrimidine CDK2 inhibitor lead compounds was discovered with the new database-mining program LIDAEUS through in silico screening. Four compounds with IC(50) values ranging from 17 to 0.9 microM were selected for X-ray crystal analysis. Two distinct binding modes are observed, one of which resembles the hydrogen bonding pattern of bound ATP. In the second binding mode, the ligands trigger a conformational change in the activation T loop by inducing movement of Lys(33) and Asp(145) side chains. The family of molecules discovered provides an excellent starting point for the design and synthesis of tight binding inhibitors, which may lead to a new class of antiproliferative drugs.
About this Structure
1PXL is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop., Wu SY, McNae I, Kontopidis G, McClue SJ, McInnes C, Stewart KJ, Wang S, Zheleva DI, Marriage H, Lane DP, Taylor P, Fischer PM, Walkinshaw MD, Structure. 2003 Apr;11(4):399-410. PMID:12679018
Page seeded by OCA on Thu Feb 21 14:33:34 2008
Categories: Homo sapiens | Single protein | Fischer, P M. | Kontopidis, G. | Lane, D P. | Marriage, H. | McClue, S J. | McInnes, C. | McNae, I. | Stewart, K J. | Taylor, P. | Walkinshaw, M D. | Wang, S. | Wu, S Y. | Zheleva, D I. | CK4 | 3d-structure. | Atp-binding | Cell cycle | Cell division | Inhibition | Mitosis | Phosphorylation | Protein kinase | Serine/threonine-protein kinase | Transferase
