1nmk

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[[Image:1nmk.png|left|200px]]
 
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==The Sanglifehrin-Cyclophilin Interaction: Degradation Work, Synthetic Macrocyclic Analogues, X-ray Crystal Structure and Binding Data==
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The line below this paragraph, containing "STRUCTURE_1nmk", creates the "Structure Box" on the page.
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<StructureSection load='1nmk' size='340' side='right'caption='[[1nmk]], [[Resolution|resolution]] 2.10&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'>[[1nmk]] is a 2 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=1NMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NMK 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]] 2.1&#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=SFM:(13E,15E)-(3S,6S,9R,10R,11S,12S,18S,21S)-10,12-DIHYDROXY-3-(3-HYDROXYBEN-ZYL)-18-((E)-3-HYDROXY-1-METHYLPROPENYL)-6-ISOPROPYL-11-METHYL-9-(3-OXO-BUTYL)-19-OXA-1,4,7,25-TETRAAZA-BICYCLO[19.3.1]PENTACOSA-13,15-DIENE-2,5,8,20-TETRAONE'>SFM</scene></td></tr>
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{{STRUCTURE_1nmk| PDB=1nmk | 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=1nmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nmk OCA], [https://pdbe.org/1nmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nmk RCSB], [https://www.ebi.ac.uk/pdbsum/1nmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nmk 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/nm/1nmk_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=1nmk 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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Sanglifehrin A (SFA) is a novel immunosuppressive natural product isolated from Streptomyces sp. A92-308110. SFA has a very strong affinity for cyclophilin A (IC(50) = 6.9 +/- 0.9 nM) but is structurally different from cyclosporin A (CsA) and exerts its immunosuppressive activity via a novel mechanism. SFA has a complex molecular structure consisting of a 22-membered macrocycle, bearing in position 23 a nine-carbon tether terminated by a highly substituted spirobicyclic moiety. Selective oxidative cleavage of the C(26)=C(27) exocyclic double bond affords the spirolactam containing fragment 1 and macrolide 2. The affinity of 2 for cyclophilin (IC(50) = 29 +/- 2.1 nM) is essentially identical to SFA, which indicates that the interaction between SFA and cyclophilin A is mediated exclusively by the macrocyclic portion of the molecule. This observation was confirmed by the X-ray crystal structure resolved at 2.1 A of cyclophilin A complexed to macrolide 16, a close analogue of 2. The X-ray crystal structure showed that macrolide 16 binds to the same deep hydrophobic pocket of cyclophilin A as CsA. Additional valuable details of the structure-activity relationship were obtained by two different chemical approaches: (1) degradation work on macrolide 2 or (2) synthesis of a library of macrolide analogues using the ring-closing metathesis reaction as the key step. Altogether, it appears that the complex macrocyclic fragment of SFA is a highly optimized combination of multiple functionalities including an (E,E)-diene, a short polypropionate fragment, and an unusual tripeptide unit, which together provide an extremely strong affinity for cyclophilin A.
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===The Sanglifehrin-Cyclophilin Interaction: Degradation Work, Synthetic Macrocyclic Analogues, X-ray Crystal Structure and Binding Data===
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Sanglifehrin-cyclophilin interaction: degradation work, synthetic macrocyclic analogues, X-ray crystal structure, and binding data.,Sedrani R, Kallen J, Martin Cabrejas LM, Papageorgiou CD, Senia F, Rohrbach S, Wagner D, Thai B, Jutzi Eme AM, France J, Oberer L, Rihs G, Zenke G, Wagner J J Am Chem Soc. 2003 Apr 2;125(13):3849-59. PMID:12656618<ref>PMID:12656618</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_12656618}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1nmk" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 12656618 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12656618}}
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==About this Structure==
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[[1nmk]] 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=1NMK 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:12656618</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: Peptidylprolyl isomerase]]
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[[Category: Large Structures]]
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[[Category: Kallen, J.]]
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[[Category: Kallen J]]
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[[Category: Sedrani, R.]]
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[[Category: Sedrani R]]
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[[Category: Wagner, J.]]
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[[Category: Wagner J]]
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[[Category: Beta sandwich]]
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[[Category: Cyclophilin-ligand complex]]
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[[Category: Cyclosporin]]
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[[Category: Isomerase]]
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[[Category: Rotamase]]
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Current revision

The Sanglifehrin-Cyclophilin Interaction: Degradation Work, Synthetic Macrocyclic Analogues, X-ray Crystal Structure and Binding Data

PDB ID 1nmk

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