View source for 4znv


==Crystal Structure of the ER-alpha Ligand-binding Domain (Y537S) in complex with a 2-Methoxy-substituted OBHS derivative==
<StructureSection load='4znv' size='340' side='right'caption='[[4znv]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4znv]] 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=4ZNV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZNV 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]] 1.771&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4Q7:2-METHOXYPHENYL+(1S,2R,4S)-5,6-BIS(4-HYDROXYPHENYL)-7-OXABICYCLO[2.2.1]HEPT-5-ENE-2-SULFONATE'>4Q7</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=4znv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4znv OCA], [https://pdbe.org/4znv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4znv RCSB], [https://www.ebi.ac.uk/pdbsum/4znv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4znv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://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.
== Function ==
[https://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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Some estrogen receptor-alpha (ERalpha)-targeted breast cancer therapies such as tamoxifen have tissue-selective or cell-specific activities, while others have similar activities in different cell types. To identify biophysical determinants of cell-specific signaling and breast cancer cell proliferation, we synthesized 241 ERalpha ligands based on 19 chemical scaffolds, and compared ligand response using quantitative bioassays for canonical ERalpha activities and X-ray crystallography. Ligands that regulate the dynamics and stability of the coactivator-binding site in the C-terminal ligand-binding domain, called activation function-2 (AF-2), showed similar activity profiles in different cell types. Such ligands induced breast cancer cell proliferation in a manner that was predicted by the canonical recruitment of the coactivators NCOA1/2/3 and induction of the GREB1 proliferative gene. For some ligand series, a single inter-atomic distance in the ligand-binding domain predicted their proliferative effects. In contrast, the N-terminal coactivator-binding site, activation function-1 (AF-1), determined cell-specific signaling induced by ligands that used alternate mechanisms to control cell proliferation. Thus, incorporating systems structural analyses with quantitative chemical biology reveals how ligands can achieve distinct allosteric signaling outcomes through ERalpha.

Predictive features of ligand-specific signaling through the estrogen receptor.,Nwachukwu JC, Srinivasan S, Zheng Y, Wang S, Min J, Dong C, Liao Z, Nowak J, Wright NJ, Houtman R, Carlson KE, Josan JS, Elemento O, Katzenellenbogen JA, Zhou HB, Nettles KW Mol Syst Biol. 2016 Apr 22;12(4):864. doi: 10.15252/msb.20156701. PMID:27107013<ref>PMID:27107013</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4znv" 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: Carlson KE]]
[[Category: Cavett V]]
[[Category: Dong C]]
[[Category: Elemento O]]
[[Category: Houtman R]]
[[Category: Josan JS]]
[[Category: Katzenellenbogen JA]]
[[Category: Liao Z]]
[[Category: Min J]]
[[Category: Nettles KW]]
[[Category: Nowak J]]
[[Category: Nwachukwu JC]]
[[Category: Srinivasan S]]
[[Category: Wang S]]
[[Category: Zheng Y]]
[[Category: Zhou HB]]