View source for 5wgq


==Estrogen Receptor Alpha Ligand Binding Domain in Complex with Estradiol and SRC2-BCP1==
<StructureSection load='5wgq' size='340' side='right'caption='[[5wgq]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wgq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WGQ 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=EST:ESTRADIOL'>EST</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=5wgq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wgq OCA], [https://pdbe.org/5wgq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wgq RCSB], [https://www.ebi.ac.uk/pdbsum/5wgq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wgq ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A new computational approach to obtain quantitative energy profiles for helix folding was used in the design of orthogonal hydrocarbon and lactam bicyclic peptides. The proteolytically stable, "cross-stitched" peptide SRC2-BCP1 shows nanomolar affinity for estrogen receptor alpha and X-ray crystallography confirms a helical binding pose.

A "cross-stitched" peptide with improved helicity and proteolytic stability.,Speltz TE, Mayne CG, Fanning SW, Siddiqui Z, Tajkhorshid E, Greene GL, Moore TW Org Biomol Chem. 2018 May 23;16(20):3702-3706. doi: 10.1039/c8ob00790j. PMID:29725689<ref>PMID:29725689</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5wgq" 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: Synthetic construct]]
[[Category: Fanning SW]]
[[Category: Greene GL]]
[[Category: Mayne CG]]
[[Category: Moore TW]]
[[Category: Siddiqui Z]]
[[Category: Speltz TE]]
[[Category: Tajkhorshid E]]