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1mf8

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[[Image:1mf8.gif|left|200px]]<br /><applet load="1mf8" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1mf8, resolution 3.1&Aring;" />
 
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'''Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin'''<br />
 
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==Overview==
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==Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin==
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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.
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<StructureSection load='1mf8' size='340' side='right'caption='[[1mf8]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1mf8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Tolypocladium_inflatum Tolypocladium inflatum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MF8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MF8 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mf8 OCA], [https://pdbe.org/1mf8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mf8 RCSB], [https://www.ebi.ac.uk/pdbsum/1mf8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mf8 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PP2BA_HUMAN PP2BA_HUMAN] Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.<ref>PMID:15671020</ref> <ref>PMID:18838687</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mf/1mf8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1mf8 ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Cornea plana congenita, recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603288 603288]], Myotonic dystrophy, type 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116955 116955]]
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*[[Calcineurin 3D structures|Calcineurin 3D structures]]
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*[[Cyclophilin 3D structures|Cyclophilin 3D structures]]
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==About this Structure==
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== References ==
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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].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin., Jin L, Harrison SC, Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13522-6. Epub 2002 Sep 30. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12357034 12357034]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Phosphoprotein phosphatase]]
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[[Category: Large Structures]]
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[[Category: Protein complex]]
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[[Category: Tolypocladium inflatum]]
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[[Category: Harrison, S C.]]
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[[Category: Harrison SC]]
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[[Category: Jin, L.]]
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[[Category: Jin L]]
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[[Category: CA]]
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[[Category: PO4]]
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[[Category: immunosuppressant]]
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[[Category: protein-drug complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:40 2008''
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Current revision

Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin

PDB ID 1mf8

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