1fkj

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(New page: 200px<br /> <applet load="1fkj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fkj, resolution 1.7&Aring;" /> '''ATOMIC STRUCTURE OF ...)
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[[Image:1fkj.gif|left|200px]]<br />
 
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<applet load="1fkj" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1fkj, resolution 1.7&Aring;" />
 
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'''ATOMIC STRUCTURE OF FKBP12-FK506, AN IMMUNOPHILIN IMMUNOSUPPRESSANT COMPLEX'''<br />
 
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==Overview==
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==ATOMIC STRUCTURE OF FKBP12-FK506, AN IMMUNOPHILIN IMMUNOSUPPRESSANT COMPLEX==
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FK506 (tacrolimus) is a natural product now approved in the US and Japan, for organ transplantation. FK506, in complex with its 12 kDa cytosolic, receptor (FKBP12), is a potent agonist of immunosuppression through the, inhibition of the phosphatase activity of calcineurin. Rapamycin, (sirolimus), which is itself an immunosuppressant by a different, mechanism, completes with FK506 for binding to FKBP12 and thereby acts as, an antagonist of calcineurin inhibition. We have solved the X-ray, structure of unliganded FKBP12 and of FKBP12 in complex with FK506 and, with rapamycin; these structures show localized differences in, conformation and mobility in those regions of the protein that are known, by site-directed mutagenesis, to be involved in calcineurin inhibition. A, comparison of 16 additional X-ray structures of FKBP12 in complex with, FKBP12-binding ligands, where those structures were determined from, different crystal forms with distinct packing arrangements, lends, significance to the observed structural variability and suggests that it, represents an intrinsic functional characteristic of the protein. Similar, differences have been observed for FKBP12 before, but were considered, artifacts of crystal-packing interactions. We suggest that, immunosuppressive ligands express their differential effects in part by, modulating the conformation of FKBP12, in agreement with mutagenesis, experiments on the protein, and not simply through differences in the, ligand structures themselves.
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<StructureSection load='1fkj' size='340' side='right'caption='[[1fkj]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1fkj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FKJ 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]] 1.7&#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=FK5:8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN'>FK5</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=1fkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fkj OCA], [https://pdbe.org/1fkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fkj RCSB], [https://www.ebi.ac.uk/pdbsum/1fkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fkj ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</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/fk/1fkj_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=1fkj ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1FKJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FK5 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1FKJ OCA].
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*[[FKBP 3D structures|FKBP 3D structures]]
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== References ==
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==Reference==
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<references/>
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Comparative X-ray structures of the major binding protein for the immunosuppressant FK506 (tacrolimus) in unliganded form and in complex with FK506 and rapamycin., Wilson KP, Yamashita MM, Sintchak MD, Rotstein SH, Murcko MA, Boger J, Thomson JA, Fitzgibbon MJ, Black JR, Navia MA, Acta Crystallogr D Biol Crystallogr. 1995 Jul 1;51(Pt 4):511-21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15299838 15299838]
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Peptidylprolyl isomerase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Navia MA]]
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[[Category: Navia, M.A.]]
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[[Category: Sintchak MD]]
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[[Category: Sintchak, M.D.]]
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[[Category: Thomson JA]]
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[[Category: Thomson, J.A.]]
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[[Category: Wilson KP]]
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[[Category: Wilson, K.P.]]
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[[Category: FK5]]
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[[Category: cis-trans prolyl-isomerase]]
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[[Category: fk506 binding protein]]
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[[Category: fkbp12]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:54:20 2007''
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Current revision

ATOMIC STRUCTURE OF FKBP12-FK506, AN IMMUNOPHILIN IMMUNOSUPPRESSANT COMPLEX

PDB ID 1fkj

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