1yat
From Proteopedia
(New page: 200px<br /> <applet load="1yat" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yat, resolution 2.5Å" /> '''IMPROVED CALCINEURIN...) |
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| - | [[Image:1yat. | + | [[Image:1yat.jpg|left|200px]]<br /><applet load="1yat" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1yat, resolution 2.5Å" /> | caption="1yat, resolution 2.5Å" /> | ||
'''IMPROVED CALCINEURIN INHIBITION BY YEAST FKBP12-DRUG COMPLEXES. CRYSTALLOGRAPHIC AND FUNCTIONAL ANALYSIS'''<br /> | '''IMPROVED CALCINEURIN INHIBITION BY YEAST FKBP12-DRUG COMPLEXES. CRYSTALLOGRAPHIC AND FUNCTIONAL ANALYSIS'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1YAT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with FK5 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1YAT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=FK5:'>FK5</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YAT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: binding protein]] | [[Category: binding protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:11:22 2008'' |
Revision as of 15:11, 15 February 2008
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IMPROVED CALCINEURIN INHIBITION BY YEAST FKBP12-DRUG COMPLEXES. CRYSTALLOGRAPHIC AND FUNCTIONAL ANALYSIS
Overview
The protein phosphatase calcineurin is the putative target for the, immunosuppressive drug FK-506. The enzyme is inhibited by the complex of, the drug with its intracellular receptor, the 12-kDa FK-506-binding, protein (FKBP12), and the strength of inhibition usually correlates, strongly with immunosuppressive potency. We find, however, that the, complex of yeast FKBP12 with L-685,818, a well characterized antagonist of, FK-506 immunosuppression, is a potent inhibitor of calcineurin. The, corresponding human complex does not inhibit the enzyme, and both human, and yeast complexes with FK-506 do inhibit. To understand the structural, basis of these findings, we have determined the three-dimensional, structure of the complex of yeast FKBP12 with FK-506 by x-ray, crystallography, and have found that the structure of the yeast complex is, strikingly similar to its human homolog. These observations indicate that, specific sequence elements in the yeast protein provide stronger binding, interactions with a heterologous calcineurin than do the corresponding, elements in the human protein, and suggest structural modifications that, may improve the potency of this class of immunosuppressants.
About this Structure
1YAT is a Single protein structure of sequence from Saccharomyces cerevisiae with as ligand. Full crystallographic information is available from OCA.
Reference
Improved calcineurin inhibition by yeast FKBP12-drug complexes. Crystallographic and functional analysis., Rotonda J, Burbaum JJ, Chan HK, Marcy AI, Becker JW, J Biol Chem. 1993 Apr 15;268(11):7607-9. PMID:7681823
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