1t4e
From Proteopedia
(New page: 200px<br /> <applet load="1t4e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t4e, resolution 2.60Å" /> '''Structure of Human ...) |
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| - | [[Image:1t4e.gif|left|200px]]<br /> | + | [[Image:1t4e.gif|left|200px]]<br /><applet load="1t4e" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1t4e" size=" | + | |
caption="1t4e, resolution 2.60Å" /> | caption="1t4e, resolution 2.60Å" /> | ||
'''Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor'''<br /> | '''Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting | + | HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53. |
==About this Structure== | ==About this Structure== | ||
| - | 1T4E 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 DIZ as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1T4E 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=DIZ:'>DIZ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T4E OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carver, T | + | [[Category: Carver, T E.]] |
| - | [[Category: Franks, C | + | [[Category: Franks, C F.]] |
| - | [[Category: Grasberger, B | + | [[Category: Grasberger, B L.]] |
| - | [[Category: Koblish, H | + | [[Category: Koblish, H K.]] |
| - | [[Category: LaFrance, L | + | [[Category: LaFrance, L V.]] |
[[Category: Lu, T.]] | [[Category: Lu, T.]] | ||
| - | [[Category: Parks, D | + | [[Category: Parks, D J.]] |
[[Category: Schubert, C.]] | [[Category: Schubert, C.]] | ||
| - | [[Category: Zhao, S | + | [[Category: Zhao, S Y.]] |
[[Category: DIZ]] | [[Category: DIZ]] | ||
[[Category: mdm2-inhibitor complex]] | [[Category: mdm2-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:45 2008'' |
Revision as of 13:09, 21 February 2008
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Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor
Overview
HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53.
About this Structure
1T4E is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells., Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicz KL, Calvo RR, Maguire D, Lattanze J, Franks CF, Zhao S, Ramachandren K, Bylebyl GR, Zhang M, Manthey CL, Petrella EC, Pantoliano MW, Deckman IC, Spurlino JC, Maroney AC, Tomczuk BE, Molloy CJ, Bone RF, J Med Chem. 2005 Feb 24;48(4):909-12. PMID:15715460
Page seeded by OCA on Thu Feb 21 15:09:45 2008
