1g5s
From Proteopedia
(New page: 200px<br /> <applet load="1g5s" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g5s, resolution 2.61Å" /> '''CRYSTAL STRUCTURE O...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1g5s.gif|left|200px]]<br /> | + | [[Image:1g5s.gif|left|200px]]<br /><applet load="1g5s" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1g5s" size=" | + | |
caption="1g5s, resolution 2.61Å" /> | caption="1g5s, resolution 2.61Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH THE INHIBITOR H717'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH THE INHIBITOR H717'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic | + | Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A resolution. The orientation of the C2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs. |
==About this Structure== | ==About this Structure== | ||
| - | 1G5S 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 I17 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1G5S 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=I17:'>I17</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G5S OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 13: | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bitonti, A | + | [[Category: Bitonti, A J.]] |
| - | [[Category: Borcherding, D | + | [[Category: Borcherding, D R.]] |
| - | [[Category: Dreyer, M | + | [[Category: Dreyer, M K.]] |
| - | [[Category: Dumont, J | + | [[Category: Dumont, J A.]] |
| - | [[Category: Kim, S | + | [[Category: Kim, S H.]] |
| - | [[Category: Peet, N | + | [[Category: Peet, N P.]] |
[[Category: Shen, J.]] | [[Category: Shen, J.]] | ||
| - | [[Category: Tsay, J | + | [[Category: Tsay, J T.]] |
| - | [[Category: Wright, P | + | [[Category: Wright, P S.]] |
[[Category: I17]] | [[Category: I17]] | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:46:27 2008'' |
Revision as of 10:46, 21 February 2008
|
CRYSTAL STRUCTURE OF HUMAN CYCLIN DEPENDENT KINASE 2 (CDK2) IN COMPLEX WITH THE INHIBITOR H717
Overview
Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A resolution. The orientation of the C2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.
About this Structure
1G5S is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717., Dreyer MK, Borcherding DR, Dumont JA, Peet NP, Tsay JT, Wright PS, Bitonti AJ, Shen J, Kim SH, J Med Chem. 2001 Feb 15;44(4):524-30. PMID:11170642
Page seeded by OCA on Thu Feb 21 12:46:27 2008
