View source for 4xnc


==Crystal structure at room temperature of cyclophilin D in complex with an inhibitor==
<StructureSection load='4xnc' size='340' side='right' caption='[[4xnc]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4xnc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XNC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XNC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EA4:ETHYL+N-[(4-AMINOBENZYL)CARBAMOYL]GLYCINATE'>EA4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xnc OCA], [http://pdbe.org/4xnc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xnc RCSB], [http://www.ebi.ac.uk/pdbsum/4xnc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xnc ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4xnc" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclophilin|Cyclophilin]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Peptidylprolyl isomerase]]
[[Category: Allemand, F]]
[[Category: Gelin, M]]
[[Category: Guichou, J F]]
[[Category: Labesse, G]]
[[Category: Inhibitor isomerase fragment based drug design]]
[[Category: Isomerase]]