4mg5
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4mg5 is ON HOLD Authors: DELFOSSE, V., GRIMALDI, M., BOURGUET, W. Description: Crystal structure of hERa-LBD (Y537S) in complex with chlordecone) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of hERa-LBD (Y537S) in complex with chlordecone== | |
| + | <StructureSection load='4mg5' size='340' side='right'caption='[[4mg5]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4mg5]] is a 4 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=4MG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MG5 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]] 2.05Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AQV:(2~{S},3~{R},7~{R},8~{S})-1,2,3,4,6,7,8,9,10,10-decakis(chloranyl)pentacyclo[5.3.0.0^{2,6}.0^{3,9}.0^{4,8}]decane-5,5-diol'>A1AQV</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4mg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mg5 OCA], [https://pdbe.org/4mg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mg5 RCSB], [https://www.ebi.ac.uk/pdbsum/4mg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mg5 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BACKGROUND: Individuals are exposed daily to environmental pollutants which may act as endocrine-disrupting chemicals (EDCs) causing a range of developmental, reproductive, metabolic or neoplastic diseases. With their mostly hydrophobic pocket that serves as a docking site for endogenous and exogenous ligands, nuclear receptors (NRs) can be primary targets of small molecule environmental contaminants. However, most of these compounds are chemically unrelated to natural hormones so their binding modes and associated hormonal activities are hardly predictable. OBJECTIVES: We conducted a correlative analysis of structural and functional data to gain insight into the mechanisms by which twelve members of representative families of pollutants bind to and activate the estrogen receptors ERalpha and ERbeta. METHODS: We have used a battery of biochemical, structural, biophysical and cell-based approaches to characterize the interaction between ERs and their environmental ligands. RESULTS: Our study reveals that the chemically diverse compounds bind to ERs via varied sets of protein ligand interactions reflecting their differential activities, binding affinities and specificities. We show that xenoestrogens bind to both ERs with affinities ranging from sub nanomolar to micromolar values and act in a subtype-dependent fashion as full agonists or partial agonists/antagonists by using different combinations of the activation functions 1 and 2 of ERalpha and ERbeta. CONCLUSIONS: The precise characterization of the interactions between major environmental pollutants and two of their primary biological targets provides rational guidelines for the design of safer chemicals and will increase the accuracy and usefulness of structure-based computational methods, allowing for activity prediction of chemicals in risk assessment. | ||
| - | + | Structural and Functional Profiling of Environmental Ligands for Estrogen Receptors.,Delfosse V, Grimaldi M, Cavailles V, Balaguer P, Bourguet W Environ Health Perspect. 2014 Sep 26. PMID:25260197<ref>PMID:25260197</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4mg5" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bourguet W]] | ||
| + | [[Category: Delfosse V]] | ||
| + | [[Category: Grimaldi M]] | ||
Current revision
Crystal structure of hERa-LBD (Y537S) in complex with chlordecone
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