4xld

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: '''Unreleased structure''' The entry 4xld is ON HOLD until Paper Publication Authors: Delfosse, V., Guichou, J.-F. Description: Crystal structure of the human PPARg-LBD/rosiglitazone c...)
Current revision (10:49, 10 January 2024) (edit) (undo)
 
(6 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 4xld is ON HOLD until Paper Publication
+
==Crystal structure of the human PPARg-LBD/rosiglitazone complex obtained by dry co-crystallization and in situ diffraction==
 +
<StructureSection load='4xld' size='340' side='right'caption='[[4xld]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4xld]] 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=4XLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XLD 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]] 2.45&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BRL:2,4-THIAZOLIDIINEDIONE,+5-[[4-[2-(METHYL-2-PYRIDINYLAMINO)ETHOXY]PHENYL]METHYL]-(9CL)'>BRL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=4xld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xld OCA], [https://pdbe.org/4xld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xld RCSB], [https://www.ebi.ac.uk/pdbsum/4xld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xld ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Note=Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9753710</ref> Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:[https://omim.org/entry/604367 604367]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.<ref>PMID:12453919</ref> <ref>PMID:11788685</ref> Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:[https://omim.org/entry/137800 137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</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.
-
Authors: Delfosse, V., Guichou, J.-F.
+
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>
-
Description: Crystal structure of the human PPARg-LBD/rosiglitazone complex obtained by dry co-crystallization and in situ diffraction
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Guichou, J.-F]]
+
<div class="pdbe-citations 4xld" style="background-color:#fffaf0;"></div>
-
[[Category: Delfosse, V]]
+
 
 +
==See Also==
 +
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Delfosse V]]
 +
[[Category: Guichou J-F]]

Current revision

Crystal structure of the human PPARg-LBD/rosiglitazone complex obtained by dry co-crystallization and in situ diffraction

PDB ID 4xld

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xld"
Personal tools