1mf8: Difference between revisions

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New page: left|200px<br /> <applet load="1mf8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mf8, resolution 3.1Å" /> '''Crystal Structure of...
 
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[[Image:1mf8.gif|left|200px]]<br />
[[Image:1mf8.gif|left|200px]]<br /><applet load="1mf8" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="1mf8" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="1mf8, resolution 3.1&Aring;" />
caption="1mf8, resolution 3.1&Aring;" />
'''Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin'''<br />
'''Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin'''<br />


==Overview==
==Overview==
Calcineurin (Cn), a Ca(2+)/calmodulin-dependent Ser/Thr protein, phosphatase, is an important participant in signaling pathways that, activate T cells. It is the target of the immunosuppressive drugs, cyclosporin A (CsA) and FK506. These drugs bind proteins known as, cyclophilin (Cyp) and FK506-binding protein, respectively, and the, drug-protein complexes in turn inhibit Cn. We report the crystal structure, of a Cyp/CsA/Cn ternary complex, determined to a resolution of 3.1 A., Residues 3-9 of CsA, particularly N-methyl leucines 4 and 6, and Trp-121, of Cyp form a composite surface for interaction with Cn. The hydrophobic, interface buries two hydrogen bonds. The structure accounts clearly for, the effects of mutations in Cn on CsA-resistance and for the way, modifications of CsA alter immunosuppressive activity.
Calcineurin (Cn), a Ca(2+)/calmodulin-dependent Ser/Thr protein phosphatase, is an important participant in signaling pathways that activate T cells. It is the target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. These drugs bind proteins known as cyclophilin (Cyp) and FK506-binding protein, respectively, and the drug-protein complexes in turn inhibit Cn. We report the crystal structure of a Cyp/CsA/Cn ternary complex, determined to a resolution of 3.1 A. Residues 3-9 of CsA, particularly N-methyl leucines 4 and 6, and Trp-121 of Cyp form a composite surface for interaction with Cn. The hydrophobic interface buries two hydrogen bonds. The structure accounts clearly for the effects of mutations in Cn on CsA-resistance and for the way modifications of CsA alter immunosuppressive activity.


==Disease==
==Disease==
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==About this Structure==
==About this Structure==
1MF8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and PO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1MF8 OCA].  
1MF8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MF8 OCA].  


==Reference==
==Reference==
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[[Category: Phosphoprotein phosphatase]]
[[Category: Phosphoprotein phosphatase]]
[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Harrison, S.C.]]
[[Category: Harrison, S C.]]
[[Category: Jin, L.]]
[[Category: Jin, L.]]
[[Category: CA]]
[[Category: CA]]
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[[Category: protein-drug complex]]
[[Category: protein-drug complex]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:10:35 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:40 2008''