4zsc: Difference between revisions
New page: '''Unreleased structure''' The entry 4zsc is ON HOLD Authors: Gelin, M., Delfosse, V., Allemand, F., Hoh, F., Sallaz-Damaz, Y., Pirocchi, M., Bourguet, W., Ferrer, J.-L., Labesse, G., G... |
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==Human Cyclophilin D Complexed with an Inhibitor at room temperature== | |||
<StructureSection load='4zsc' size='340' side='right'caption='[[4zsc]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4zsc]] 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=4ZSC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZSC FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zsc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsc OCA], [https://pdbe.org/4zsc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zsc RCSB], [https://www.ebi.ac.uk/pdbsum/4zsc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsc ProSAT]</span></td></tr> | |||
</table> | |||
== 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;"> | |||
== Publication Abstract from PubMed == | |||
X-ray crystallography is an established technique for ligand screening in fragment-based drug-design projects, but the required manual handling steps - soaking crystals with ligand and the subsequent harvesting - are tedious and limit the throughput of the process. Here, an alternative approach is reported: crystallization plates are pre-coated with potential binders prior to protein crystallization and X-ray diffraction is performed directly `in situ' (or in-plate). Its performance is demonstrated on distinct and relevant therapeutic targets currently being studied for ligand screening by X-ray crystallography using either a bending-magnet beamline or a rotating-anode generator. The possibility of using DMSO stock solutions of the ligands to be coated opens up a route to screening most chemical libraries. | |||
Combining `dry' co-crystallization and in situ diffraction to facilitate ligand screening by X-ray crystallography.,Gelin M, Delfosse V, Allemand F, Hoh F, Sallaz-Damaz Y, Pirocchi M, Bourguet W, Ferrer JL, Labesse G, Guichou JF Acta Crystallogr D Biol Crystallogr. 2015 Aug 1;71(Pt 8):1777-87. doi:, 10.1107/S1399004715010342. Epub 2015 Jul 31. PMID:26249358<ref>PMID:26249358</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4zsc" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Cyclophilin 3D structures|Cyclophilin 3D structures]] | ||
[[Category: | == References == | ||
[[Category: Gelin | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Pirocchi | [[Category: Large Structures]] | ||
[[Category: Allemand F]] | |||
[[Category: Bourguet W]] | |||
[[Category: Delfosse V]] | |||
[[Category: Ferrer J-L]] | |||
[[Category: Gelin M]] | |||
[[Category: Guichou J-F]] | |||
[[Category: Hoh F]] | |||
[[Category: Labesse G]] | |||
[[Category: Pirocchi M]] | |||
[[Category: Sallaz-Damaz Y]] | |||
Latest revision as of 14:33, 9 May 2024
Human Cyclophilin D Complexed with an Inhibitor at room temperatureHuman Cyclophilin D Complexed with an Inhibitor at room temperature
Structural highlights
FunctionPPIF_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 PubMedX-ray crystallography is an established technique for ligand screening in fragment-based drug-design projects, but the required manual handling steps - soaking crystals with ligand and the subsequent harvesting - are tedious and limit the throughput of the process. Here, an alternative approach is reported: crystallization plates are pre-coated with potential binders prior to protein crystallization and X-ray diffraction is performed directly `in situ' (or in-plate). Its performance is demonstrated on distinct and relevant therapeutic targets currently being studied for ligand screening by X-ray crystallography using either a bending-magnet beamline or a rotating-anode generator. The possibility of using DMSO stock solutions of the ligands to be coated opens up a route to screening most chemical libraries. Combining `dry' co-crystallization and in situ diffraction to facilitate ligand screening by X-ray crystallography.,Gelin M, Delfosse V, Allemand F, Hoh F, Sallaz-Damaz Y, Pirocchi M, Bourguet W, Ferrer JL, Labesse G, Guichou JF Acta Crystallogr D Biol Crystallogr. 2015 Aug 1;71(Pt 8):1777-87. doi:, 10.1107/S1399004715010342. Epub 2015 Jul 31. PMID:26249358[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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