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1yat

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{{STRUCTURE_1yat| PDB=1yat | SCENE= }}
{{STRUCTURE_1yat| PDB=1yat | SCENE= }}
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'''IMPROVED CALCINEURIN INHIBITION BY YEAST FKBP12-DRUG COMPLEXES. CRYSTALLOGRAPHIC AND FUNCTIONAL ANALYSIS'''
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===IMPROVED CALCINEURIN INHIBITION BY YEAST FKBP12-DRUG COMPLEXES. CRYSTALLOGRAPHIC AND FUNCTIONAL ANALYSIS===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_7681823}}
==About this Structure==
==About this Structure==
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[[Category: Rotonda, J.]]
[[Category: Rotonda, J.]]
[[Category: Binding protein]]
[[Category: Binding protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:05:22 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:26:22 2008''

Revision as of 21:26, 28 July 2008

Image:1yat.png

Template:STRUCTURE 1yat

IMPROVED CALCINEURIN INHIBITION BY YEAST FKBP12-DRUG COMPLEXES. CRYSTALLOGRAPHIC AND FUNCTIONAL ANALYSIS

Template:ABSTRACT PUBMED 7681823

About this Structure

1YAT is a Single protein structure of sequence from Saccharomyces cerevisiae. 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

Page seeded by OCA on Tue Jul 29 00:26:22 2008

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