1cwb

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[[Image:1cwb.png|left|200px]]
 
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==THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY==
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The line below this paragraph, containing "STRUCTURE_1cwb", creates the "Structure Box" on the page.
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<StructureSection load='1cwb' size='340' side='right'caption='[[1cwb]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1cwb]] is a 2 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=1CWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CWB FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.2&#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=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DMT:3-HYDROXY-4,4-DIMETHYL-2-(METHYLAMINO)-6-OCTENOIC+ACID'>DMT</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene></td></tr>
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{{STRUCTURE_1cwb| PDB=1cwb | SCENE= }}
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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=1cwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cwb OCA], [https://pdbe.org/1cwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cwb RCSB], [https://www.ebi.ac.uk/pdbsum/1cwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cwb ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
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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/cw/1cwb_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=1cwb ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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For most of the cyclosporin A (CsA) analogs, there is generally a good correlation between cyclophilin binding and immunosuppression. However, this relationship does not seem to hold for 4-[(E)-2-butenyl]-4,4,N-trimethyl-L-threonine1 (MeBm2t)1-CsA. Its affinity for cyclophilin was reported to be approximately 1% that of CsA and its immunosuppressive activity in vitro was shown to be approximately 30% that of CsA. We report here the crystal structure of a complex between recombinant human cyclophilin A (CypA) and (MeBm2t)1-CsA which has been determined by X-ray crystallography at 2.2 A resolution and refined to an R-factor of 16.3%. (MeBm2t)1-CsA shows a similar bound conformation and network of interactions to CypA as CsA. The measured lower affinity for CypA cannot therefore be explained by a different mode of binding. We propose that the poor affinity to CypA could be accounted for by the existence of an equilibrium in aqueous solution between a 'cyclophilin bound conformation' and a 'non-binding conformation' of (MeBm2t)1-CsA. The relatively high immunosuppressive activity is suggested to result from slight conformational differences observed in the effector domain.
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===THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY===
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The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity.,Mikol V, Kallen J, Walkinshaw MD Protein Eng. 1994 May;7(5):597-603. PMID:8073029<ref>PMID:8073029</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_8073029}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1cwb" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 8073029 is the PubMed ID number.
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{{ABSTRACT_PUBMED_8073029}}
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==About this Structure==
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[[1cwb]] is a 2 chain structure of [[Cyclophilin]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CWB OCA].
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==See Also==
==See Also==
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*[[Cyclophilin]]
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*[[Cyclophilin 3D structures|Cyclophilin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:8073029</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Kallen, J.]]
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[[Category: Large Structures]]
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[[Category: Mikol, V.]]
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[[Category: Tolypocladium inflatum]]
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[[Category: Walkinshaw, M D.]]
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[[Category: Kallen J]]
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[[Category: Mikol V]]
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[[Category: Walkinshaw MD]]

Current revision

THE X-RAY STRUCTURE OF (MEBM2T)1-CYCLOSPORIN COMPLEXED WITH CYCLOPHILIN A PROVIDES AN EXPLANATION FOR ITS ANOMALOUSLY HIGH IMMUNOSUPPRESSIVE ACTIVITY

PDB ID 1cwb

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