5gtr

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "5gtr" [edit=sysop:move=sysop])
Current revision (11:42, 2 August 2023) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 5gtr is ON HOLD
+
==estrogen receptor alpha in complex with a stabilized peptide antagonist 6==
 +
<StructureSection load='5gtr' size='340' side='right'caption='[[5gtr]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[5gtr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GTR 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]] 2.804&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JY:4-METHYL-L-LEUCINE'>0JY</scene>, <scene name='pdbligand=DPP:DIAMINOPROPANOIC+ACID'>DPP</scene>, <scene name='pdbligand=EST:ESTRADIOL'>EST</scene>, <scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</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=5gtr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtr OCA], [https://pdbe.org/5gtr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gtr RCSB], [https://www.ebi.ac.uk/pdbsum/5gtr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtr 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 ==
 +
Direct inhibition of the protein-protein interaction of ERalpha and its endogenous coactivators with a cell permeable stabilized peptide may offer a novel, promising strategy for combating ERalpha positive breast cancers. Here, we report the co-crystal structure of a helical peptide stabilized by a N-terminal unnatural cross-linked aspartic acid (TD) in complex with the ERalpha ligand binding domain (LBD). We designed a series of peptides and peptide 6 that showed direct and high-affinity binding to ERalpha with selective antiproliferative activity in ERalpha positive breast cancer cells. The co-crystal structure of the TD-stabilized peptide 6 in complex with ERalpha LBD further demonstrates that it forms an alpha helical conformation and directly binds at the coactivator binding site of ERalpha. Further studies showed that peptide 6W could potently inhibit cellular ERalpha's transcriptional activity. This approach demonstrates the potential of TD stabilized peptides to modulate various intracellular protein-protein interactions involved in a range of disorders.
-
Authors: Xie, M., Wang, T., Li, Z.-G.
+
Structural Basis of Inhibition of ERalpha-Coactivator Interaction by High-Affinity N-Terminus Isoaspartic Acid Tethered Helical Peptides.,Xie M, Zhao H, Liu Q, Zhu Y, Yin F, Liang Y, Jiang Y, Wang D, Hu K, Qin X, Wang Z, Wu Y, Xu N, Ye X, Wang T, Li Z J Med Chem. 2017 Nov 9;60(21):8731-8740. doi: 10.1021/acs.jmedchem.7b00732. Epub , 2017 Oct 31. PMID:29045135<ref>PMID:29045135</ref>
-
Description: estrogen receptor alpha in complex with a stabilized peptide antagonist 6
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Li, Z.-G]]
+
<div class="pdbe-citations 5gtr" style="background-color:#fffaf0;"></div>
-
[[Category: Wang, T]]
+
 
-
[[Category: Xie, M]]
+
==See Also==
 +
*[[Estrogen receptor 3D structures|Estrogen receptor 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Unidentified]]
 +
[[Category: Li Z-G]]
 +
[[Category: Wang T]]
 +
[[Category: Xie M]]

Current revision

estrogen receptor alpha in complex with a stabilized peptide antagonist 6

PDB ID 5gtr

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5gtr"
Personal tools