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| | <StructureSection load='3rdd' size='340' side='right'caption='[[3rdd]], [[Resolution|resolution]] 2.14Å' scene=''> | | <StructureSection load='3rdd' size='340' side='right'caption='[[3rdd]], [[Resolution|resolution]] 2.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rdd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RDD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RDD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rdd]] 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=3RDD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RDD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EA4:ETHYL+N-[(4-AMINOBENZYL)CARBAMOYL]GLYCINATE'>EA4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.14Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3r49|3r49]], [[3r4g|3r4g]], [[3r54|3r54]], [[3r56|3r56]], [[3r57|3r57]], [[3r59|3r59]], [[3rcf|3rcf]], [[3rcg|3rcg]], [[3rci|3rci]], [[3rck|3rck]], [[3rcl|3rcl]], [[3rd9|3rd9]], [[3rda|3rda]], [[3rdb|3rdb]], [[3rdc|3rdc]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EA4:ETHYL+N-[(4-AMINOBENZYL)CARBAMOYL]GLYCINATE'>EA4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPIA, CYPA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rdd OCA], [https://pdbe.org/3rdd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rdd RCSB], [https://www.ebi.ac.uk/pdbsum/3rdd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rdd ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rdd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rdd OCA], [https://pdbe.org/3rdd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rdd RCSB], [https://www.ebi.ac.uk/pdbsum/3rdd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rdd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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.
| + | [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. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Cyclophilins are peptidyl-prolyl cis/trans isomerases (PPIase) that catalyse the interconversion of the peptide bond at proline residues. Several cyclophilins play a pivotal role in the life cycle of a number of viruses. The existing cyclophilin inhibitors, all derived from cyclosporine A or sanglifehrin A, have disadvantages, including their size, potential for side effects unrelated to cyclophilin inhibition and drug-drug interactions, unclear antiviral spectrum and manufacturing issues. Here we use a fragment-based drug discovery approach using nucleic magnetic resonance, X-ray crystallography and structure-based compound optimization to generate a new family of non-peptidic, small-molecule cyclophilin inhibitors with potent in vitro PPIase inhibitory activity and antiviral activity against hepatitis C virus, human immunodeficiency virus and coronaviruses. This family of compounds has the potential for broad-spectrum, high-barrier-to-resistance treatment of viral infections.
| + | |
| - | | + | |
| - | Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities.,Ahmed-Belkacem A, Colliandre L, Ahnou N, Nevers Q, Gelin M, Bessin Y, Brillet R, Cala O, Douguet D, Bourguet W, Krimm I, Pawlotsky JM, Guichou JF Nat Commun. 2016 Sep 22;7:12777. doi: 10.1038/ncomms12777. PMID:27652979<ref>PMID:27652979</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3rdd" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Cyclophilin 3D structures|Cyclophilin 3D structures]] | | *[[Cyclophilin 3D structures|Cyclophilin 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peptidylprolyl isomerase]]
| + | [[Category: Ahmed-Belkacem H]] |
| - | [[Category: Ahmed-Belkacem, H]] | + | [[Category: Bessin Y]] |
| - | [[Category: Bessin, Y]] | + | [[Category: Colliandre L]] |
| - | [[Category: Colliandre, L]] | + | [[Category: Guichou JF]] |
| - | [[Category: Guichou, J F]] | + | [[Category: Pawlotsky JM]] |
| - | [[Category: Pawlotsky, J M]] | + | |
| - | [[Category: Beta barrel]]
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| - | [[Category: Cytosolic]]
| + | |
| - | [[Category: Inhibitor]]
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| - | [[Category: Isomerase-isomerase inhibitor complex]]
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| - | [[Category: Prolyl cis/trans isomerase]]
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