1rv1
From Proteopedia
(New page: 200px<br /> <applet load="1rv1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rv1, resolution 2.30Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1rv1.gif|left|200px]]<br /> | + | [[Image:1rv1.gif|left|200px]]<br /><applet load="1rv1" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1rv1" size=" | + | |
caption="1rv1, resolution 2.30Å" /> | caption="1rv1, resolution 2.30Å" /> | ||
'''CRYSTAL STRUCTURE OF HUMAN MDM2 WITH AN IMIDAZOLINE INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN MDM2 WITH AN IMIDAZOLINE INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | MDM2 binds the p53 tumor suppressor protein with high affinity and | + | MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice. |
==About this Structure== | ==About this Structure== | ||
| - | 1RV1 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 IMZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1RV1 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=IMZ:'>IMZ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RV1 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-protein interaction]] | [[Category: protein-protein interaction]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:54:53 2008'' |
Revision as of 12:54, 21 February 2008
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CRYSTAL STRUCTURE OF HUMAN MDM2 WITH AN IMIDAZOLINE INHIBITOR
Overview
MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes. These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice.
About this Structure
1RV1 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
In vivo activation of the p53 pathway by small-molecule antagonists of MDM2., Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA, Science. 2004 Feb 6;303(5659):844-8. Epub 2004 Jan 2. PMID:14704432
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