View source for 5kcu


==Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in Complex with an N-ethyl, alpha-naphthyl OBHS-N derivative==
<StructureSection load='5kcu' size='340' side='right' caption='[[5kcu]], [[Resolution|resolution]] 2.03&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kcu]] is a 4 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5bp6 5bp6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KCU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KCU FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=OB8:(1S,2R,4S)-N-ETHYL-5,6-BIS(4-HYDROXYPHENYL)-N-(NAPHTHALEN-2-YL)-7-OXABICYCLO[2.2.1]HEPT-5-ENE-2-SULFONAMIDE'>OB8</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kcc|5kcc]], [[5kcd|5kcd]], [[5kcf|5kcf]], [[5kct|5kct]], [[5kcw|5kcw]], [[5kd9|5kd9]]</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kcu OCA], [http://pdbe.org/5kcu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kcu RCSB], [http://www.ebi.ac.uk/pdbsum/5kcu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kcu ProSAT]</span></td></tr>
</table>
== Function ==
[[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>  
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Boonmuen, N]]
[[Category: Bruno, N E]]
[[Category: Dharmarajan, V]]
[[Category: Frasor, J]]
[[Category: Goswami, D]]
[[Category: Griffin, P R]]
[[Category: Kastrati, I]]
[[Category: Katzenellenbogen, B S]]
[[Category: Katzenellenbogen, J A]]
[[Category: Min, J]]
[[Category: Nettles, K W]]
[[Category: Novick, S]]
[[Category: Nowak, J]]
[[Category: Nwachukwu, J C]]
[[Category: Srinivasan, S]]
[[Category: Zhao, Y]]
[[Category: Zhou, H B]]
[[Category: Ligand binding]]
[[Category: Nuclear receptor]]
[[Category: Protein-ligand complex]]
[[Category: Transcription]]
[[Category: Transcription factor]]