3rcg: Difference between revisions
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==Human cyclophilin D complexed with dimethylformamide== | ==Human cyclophilin D complexed with dimethylformamide== | ||
<StructureSection load='3rcg' size='340' side='right' caption='[[3rcg]], [[Resolution|resolution]] 0.97Å' scene=''> | <StructureSection load='3rcg' size='340' side='right'caption='[[3rcg]], [[Resolution|resolution]] 0.97Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3rcg]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3rcg]] 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=3RCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RCG FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r49|3r49]], [[3r4g|3r4g]], [[3r54|3r54]], [[3r56|3r56]], [[3r57|3r57]], [[3r59|3r59]], [[3rcf|3rcf]], [[3rci|3rci]], [[3rck|3rck]], [[3rcl|3rcl]], [[3rd9|3rd9]], [[3rda|3rda]], [[3rdb|3rdb]], [[3rdc|3rdc]], [[3rdd|3rdd]]</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]], [[3rci|3rci]], [[3rck|3rck]], [[3rcl|3rcl]], [[3rd9|3rd9]], [[3rda|3rda]], [[3rdb|3rdb]], [[3rdc|3rdc]], [[3rdd|3rdd]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPIF, CYP3 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPIF, CYP3 ([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'>[ | <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rcg OCA], [https://pdbe.org/3rcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rcg RCSB], [https://www.ebi.ac.uk/pdbsum/3rcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rcg ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/PPIF_HUMAN PPIF_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probablity of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.<ref>PMID:19228691</ref> <ref>PMID:22726440</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Cyclophilin|Cyclophilin]] | *[[Cyclophilin 3D structures|Cyclophilin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Peptidylprolyl isomerase]] | [[Category: Peptidylprolyl isomerase]] | ||
[[Category: Ahmed-Belkacem, H]] | [[Category: Ahmed-Belkacem, H]] | ||
Revision as of 08:57, 15 June 2022
Human cyclophilin D complexed with dimethylformamideHuman cyclophilin D complexed with dimethylformamide
Structural highlights
Function[PPIF_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probablity of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.[1] [2] Publication Abstract from PubMedCyclophilins 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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