2p15: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2p15.gif|left|200px]]<br /><applet load="2p15" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="2p15, resolution 1.940&Aring;" />
-'''Crystal structure of the ER alpha ligand binding domain with the agonist ortho-trifluoromethylphenylvinyl estradiol'''<br />
-==Overview==
+==Crystal structure of the ER alpha ligand binding domain with the agonist ortho-trifluoromethylphenylvinyl estradiol==
-The steroid hormone receptors are characterized by binding to relatively, rigid, inflexible endogenous steroid ligands. Other members of the nuclear, receptor superfamily bind to conformationally flexible lipids and show a, corresponding degree of elasticity in the ligand-binding pocket. Here, we, report the X-ray crystal structure of the oestrogen receptor alpha, (ERalpha) bound to an oestradiol derivative with a prosthetic group, ortho- trifluoromethlyphenylvinyl, which binds in a novel extended pocket, in the ligand-binding domain. Unlike ER antagonists with bulky side, groups, this derivative is enclosed in the ligand-binding pocket, and acts, as a potent agonist. This work shows that steroid hormone receptors can, interact with a wider array of pharmacophores than previously thought, through structural plasticity in the ligand-binding pocket.
+<StructureSection load='2p15' size='340' side='right'caption='[[2p15]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2p15]] 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=2P15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2P15 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]] 1.94&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EZT:(17BETA)-17-{(E)-2-[2-(TRIFLUOROMETHYL)PHENYL]VINYL}ESTRA-1(10),2,4-TRIENE-3,17-DIOL'>EZT</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=2p15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p15 OCA], [https://pdbe.org/2p15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2p15 RCSB], [https://www.ebi.ac.uk/pdbsum/2p15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2p15 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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p1/2p15_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2p15 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-P15 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=EZT:'>EZT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2P15 OCA].
+*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
+== References ==
-==Reference==
+<references/>
-Structural plasticity in the oestrogen receptor ligand-binding domain., Nettles KW, Bruning JB, Gil G, O'Neill EE, Nowak J, Guo Y, Kim Y, DeSombre ER, Dilis R, Hanson RN, Joachimiak A, Greene GL, EMBO Rep. 2007 Jun;8(6):563-8. Epub 2007 Apr 27. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17468738 17468738]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Bruning, J.B.]]
+[[Category: Bruning JB]]
-[[Category: Greene, G.L.]]
+[[Category: Greene GL]]
-[[Category: Kim, Y.]]
+[[Category: Kim Y]]
-[[Category: Nettles, K.W.]]
+[[Category: Nettles KW]]
-[[Category: EZT]]
-[[Category: helix 12]]
-[[Category: ligand binding domain]]
-[[Category: nulear receptor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:28:54 2008''