4pps

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==Crystal Structure of the Estrogen Receptor alpha Ligand-binding Domain in Complex with an A-CD ring estrogen derivative==
==Crystal Structure of the Estrogen Receptor alpha Ligand-binding Domain in Complex with an A-CD ring estrogen derivative==
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<StructureSection load='4pps' size='340' side='right' caption='[[4pps]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
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<StructureSection load='4pps' size='340' side='right'caption='[[4pps]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4pps]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPS OCA]. <br>
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<table><tr><td colspan='2'>[[4pps]] 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=4PPS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPS FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ESE:(1S,3AR,5R,7AS)-5-(4-HYDROXYPHENYL)-7A-METHYLOCTAHYDRO-1H-INDEN-1-OL'>ESE</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.929&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pp6|4pp6]], [[4ppp|4ppp]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ESE:(1S,3AR,5R,7AS)-5-(4-HYDROXYPHENYL)-7A-METHYLOCTAHYDRO-1H-INDEN-1-OL'>ESE</scene></td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4pps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pps OCA], [https://pdbe.org/4pps PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pps RCSB], [https://www.ebi.ac.uk/pdbsum/4pps PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pps ProSAT]</span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pps OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pps RCSB], [http://www.ebi.ac.uk/pdbsum/4pps PDBsum]</span></td></tr>
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</table>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
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== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
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[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-alpha (ERalpha) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERalpha ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFalpha genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERalpha and several ERalpha coregulators, suggesting that ERalpha functions as a primary conduit for resveratrol activity.DOI: http://dx.doi.org/10.7554/eLife.02057.001.
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Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network.,Nwachukwu JC, Srinivasan S, Bruno NE, Parent AA, Hughes TS, Pollock JA, Gjyshi O, Cavett V, Nowak J, Garcia-Ordonez RD, Houtman R, Griffin PR, Kojetin DJ, Katzenellenbogen JA, Conkright MD, Nettles KW Elife. 2014 Apr 25;3:e02057. doi: 10.7554/eLife.02057. PMID:24771768<ref>PMID:24771768</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4pps" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bruno, N E.]]
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[[Category: Homo sapiens]]
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[[Category: Cavett, V.]]
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[[Category: Large Structures]]
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[[Category: Conkright, M D.]]
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[[Category: Bruno NE]]
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[[Category: Garcia-Ordonez, R D.]]
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[[Category: Cavett V]]
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[[Category: Gjyshi, O.]]
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[[Category: Conkright MD]]
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[[Category: Griffin, P R.]]
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[[Category: Garcia-Ordonez RD]]
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[[Category: Houtman, R.]]
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[[Category: Gjyshi O]]
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[[Category: Hughes, T S.]]
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[[Category: Griffin PR]]
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[[Category: Katzenellenbogen, J A.]]
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[[Category: Houtman R]]
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[[Category: Kojetin, D J.]]
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[[Category: Hughes TS]]
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[[Category: Nettles, K W.]]
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[[Category: Katzenellenbogen JA]]
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[[Category: Nowak, J.]]
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[[Category: Kojetin DJ]]
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[[Category: Nwachukwu, J C.]]
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[[Category: Nettles KW]]
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[[Category: Parent, A A.]]
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[[Category: Nowak J]]
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[[Category: Pollock, J A.]]
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[[Category: Nwachukwu JC]]
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[[Category: Srinivasan, S.]]
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[[Category: Parent AA]]
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[[Category: Ligand-binding]]
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[[Category: Pollock JA]]
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[[Category: Nuclear hormone receptor]]
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[[Category: Srinivasan S]]
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[[Category: Nucleus]]
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[[Category: Protein binding]]
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[[Category: Transcription factor]]
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Current revision

Crystal Structure of the Estrogen Receptor alpha Ligand-binding Domain in Complex with an A-CD ring estrogen derivative

PDB ID 4pps

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