2gaq
From Proteopedia
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| - | [[Image:2gaq.gif|left|200px]] | + | [[Image:2gaq.gif|left|200px]] |
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| - | '''NMR SOLUTION STRUCTURE OF THE FRB DOMAIN OF mTOR''' | + | {{Structure |
| + | |PDB= 2gaq |SIZE=350|CAPTION= <scene name='initialview01'>2gaq</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= FRAP1, FRAP, FRAP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''NMR SOLUTION STRUCTURE OF THE FRB DOMAIN OF mTOR''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2GAQ is a [ | + | 2GAQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GAQ OCA]. |
==Reference== | ==Reference== | ||
| - | The FRB domain of mTOR: NMR solution structure and inhibitor design., Leone M, Crowell KJ, Chen J, Jung D, Chiang GG, Sareth S, Abraham RT, Pellecchia M, Biochemistry. 2006 Aug 29;45(34):10294-302. PMID:[http:// | + | The FRB domain of mTOR: NMR solution structure and inhibitor design., Leone M, Crowell KJ, Chen J, Jung D, Chiang GG, Sareth S, Abraham RT, Pellecchia M, Biochemistry. 2006 Aug 29;45(34):10294-302. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16922504 16922504] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: four helical up and down bundle]] | [[Category: four helical up and down bundle]] | ||
| - | ''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 17:02:27 2008'' |
Revision as of 15:02, 20 March 2008
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| Gene: | FRAP1, FRAP, FRAP2 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR SOLUTION STRUCTURE OF THE FRB DOMAIN OF mTOR
Overview
The mammalian target of rapamycin (mTOR) is a protein that is intricately involved in signaling pathways controlling cell growth. Rapamycin is a natural product that binds and inhibits mTOR function by interacting with its FKBP-rapamycin-binding (FRB) domain. Here we report on the NMR solution structure of FRB and on further studies aimed at the identification and characterization of novel ligands that target the rapamycin binding pocket. The biological activity of the ligands, and that of rapamycin in the absence of FKBP12, was investigated by assaying the kinase activity of mTOR. While we found that rapamycin binds the FRB domain and inhibits the kinase activity of mTOR even in the absence of FKBP12 (in the low micromolar range), our most potent ligands bind to FRB with similar binding affinity but inhibit the kinase activity of mTOR at much higher concentrations. However, we have also identified one low-affinity compound that is also capable of inhibiting mTOR. Hence, we have identified compounds that can directly mimic rapamycin or can dissociate the FRB binding from the inhibition of the catalytic activity of mTOR. As such, these ligands could be useful in deciphering the complex regulation of mTOR in the cell and in validating the FRB domain as a possible target for the development of novel therapeutic compounds.
About this Structure
2GAQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The FRB domain of mTOR: NMR solution structure and inhibitor design., Leone M, Crowell KJ, Chen J, Jung D, Chiang GG, Sareth S, Abraham RT, Pellecchia M, Biochemistry. 2006 Aug 29;45(34):10294-302. PMID:16922504
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