1ttv
From Proteopedia
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| - | [[Image:1ttv.gif|left|200px]] | + | [[Image:1ttv.gif|left|200px]] |
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| - | '''NMR Structure of a Complex Between MDM2 and a Small Molecule Inhibitor''' | + | {{Structure |
| + | |PDB= 1ttv |SIZE=350|CAPTION= <scene name='initialview01'>1ttv</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=IMY:1-{[4,5-BIS(4-CHLOROPHENYL)-2-(2-ISOPROPOXY-4-METHOXYPHENYL)-4,5-DIHYDRO-1H-IMIDAZOL-1-YL]CARBONYL}PIPERAZINE'>IMY</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= MDM2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 Xenopus laevis]) | ||
| + | }} | ||
| + | |||
| + | '''NMR Structure of a Complex Between MDM2 and a Small Molecule Inhibitor''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TTV is a [ | + | 1TTV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TTV OCA]. |
==Reference== | ==Reference== | ||
| - | NMR structure of a complex between MDM2 and a small molecule inhibitor., Fry DC, Emerson SD, Palme S, Vu BT, Liu CM, Podlaski F, J Biomol NMR. 2004 Oct;30(2):163-73. PMID:[http:// | + | NMR structure of a complex between MDM2 and a small molecule inhibitor., Fry DC, Emerson SD, Palme S, Vu BT, Liu CM, Podlaski F, J Biomol NMR. 2004 Oct;30(2):163-73. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15557803 15557803] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Xenopus laevis]] | [[Category: Xenopus laevis]] | ||
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[[Category: protein-protein interaction]] | [[Category: protein-protein interaction]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:23:04 2008'' |
Revision as of 12:23, 20 March 2008
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| Ligands: | |||||||
| Gene: | MDM2 (Xenopus laevis) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR Structure of a Complex Between MDM2 and a Small Molecule Inhibitor
Overview
MDM2 is a regulator of cell growth processes that acts by binding to the tumor suppressor protein p53 and ultimately restraining its activity. While inactivation of p53 by mutation is commonly observed in human cancers, a substantial percentage of tumors express wild type p53. In many of these cases, MDM2 is overexpressed, and it is believed that suppression of MDM2 activity could yield therapeutic benefits. Therefore, we have been focusing on the p53-MDM2 interaction as the basis of a drug discovery program and have been able to develop a series of small molecule inhibitors. We herein report a high resolution NMR structure of a complex between the p53-binding domain of MDM2 and one of these inhibitors. The form of MDM2 utilized was an engineered hybrid between the human and Xenopus sequences, which provided a favorable combination of relevancy and stability. The inhibitor is found to bind in the same site as does a highly potent peptide fragment of p53. The inhibitor is able to successfully mimic the peptide by duplicating interactions in three subpockets normally made by amino acid sidechains, and by utilizing a scaffold that presents substituents with rigidity and spatial orientation comparable to that provided by the alpha helical backbone of the peptide. The structure also suggests opportunities for modifying the inhibitor to increase its potency.
About this Structure
1TTV is a Single protein structure of sequence from Xenopus laevis. Full crystallographic information is available from OCA.
Reference
NMR structure of a complex between MDM2 and a small molecule inhibitor., Fry DC, Emerson SD, Palme S, Vu BT, Liu CM, Podlaski F, J Biomol NMR. 2004 Oct;30(2):163-73. PMID:15557803
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