2bit: Difference between revisions
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New page: left|200px<br /> <applet load="2bit" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bit, resolution 1.71Å" /> '''CRYSTAL STRUCTURE O... |
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== | ==Crystal structure of human cyclophilin D at 1.7 A resolution== | ||
In the pharmaceutical industry, knowledge of the three-dimensional | <StructureSection load='2bit' size='340' side='right'caption='[[2bit]], [[Resolution|resolution]] 1.71Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2bit]] 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=2BIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BIT 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]] 1.71Å</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=2bit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bit OCA], [https://pdbe.org/2bit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bit RCSB], [https://www.ebi.ac.uk/pdbsum/2bit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bit 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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bi/2bit_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2bit ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In the pharmaceutical industry, knowledge of the three-dimensional structure of a specific target facilitates the drug-discovery process. Despite possessing favoured analytical properties such as high purity and monodispersion in light scattering, some proteins are not capable of forming crystals suitable for X-ray analysis. Cyclophilin D, an isoform of cyclophilin that is expressed in the mitochondria, was selected as a drug target for the treatment of cardiac disorders. As the wild-type enzyme defied all attempts at crystallization, protein engineering on the enzyme surface was performed. The K133I mutant gave crystals that diffracted to 1.7 A resolution using in-house X-ray facilities and were suitable for soaking experiments. The crystals were very robust and diffraction was maintained after soaking in 25% DMSO solution: excellent conditions for the rapid analysis of complex structures including crystallographic fragment screening. | |||
Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution.,Schlatter D, Thoma R, Kung E, Stihle M, Muller F, Borroni E, Cesura A, Hennig M Acta Crystallogr D Biol Crystallogr. 2005 May;61(Pt 5):513-9. Epub 2005, Apr 20. PMID:15858260<ref>PMID:15858260</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2bit" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Cyclophilin 3D structures|Cyclophilin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Hennig M]] | |||
[[Category: Hennig | [[Category: Schlatter D]] | ||
[[Category: Schlatter | [[Category: Stihle M]] | ||
[[Category: Stihle | [[Category: Thoma R]] | ||
[[Category: Thoma | |||
