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==== | ==Crystal structure of the DNA binding domains of human transcription factor ERG, human Runx2 bound to core binding factor beta (Cbfb), and mithramycin, in complex with 16mer DNA CAGAGGATGTGGCTTC== | ||
<StructureSection load='6vgg' size='340' side='right'caption='[[6vgg]]' scene=''> | <StructureSection load='6vgg' size='340' side='right'caption='[[6vgg]], [[Resolution|resolution]] 4.31Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6vgg]] is a 5 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=6VGG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VGG FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.31Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QWP:mithramycin'>QWP</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=6vgg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vgg OCA], [https://pdbe.org/6vgg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vgg RCSB], [https://www.ebi.ac.uk/pdbsum/6vgg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vgg ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/ERG_HUMAN ERG_HUMAN] Defects in ERG are a cause of Ewing sarcoma (ES) [MIM:[https://omim.org/entry/612219 612219]. A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. Note=A chromosomal aberration involving ERG is found in patients with Erwing sarcoma. Translocation t(21;22)(q22;q12) with EWSR1. Note=Chromosomal aberrations involving ERG have been found in acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS. Translocation t(X;21)(q25-26;q22) with ELF4. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ERG_HUMAN ERG_HUMAN] Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
ETS family transcription factors of ERG and FLI1 play a key role in oncogenesis of prostate cancer and Ewing sarcoma by binding regulatory DNA sites and interfering with function of other factors. Mithramycin (MTM) is an anti-cancer, DNA binding natural product that functions as a potent antagonist of ERG and FLI1 by an unknown mechanism. We present a series of crystal structures of the DNA binding domain (DBD) of ERG/FLI1 culminating in a structure of a high-order complex of the ERG/FLI1 DBD, transcription factor Runx2, core-binding factor beta (Cbfbeta), and MTM on a DNA enhancer site, along with supporting DNA binding studies using MTM and its analogues. Taken together, these data provide insight into allosteric mechanisms underlying ERG and FLI1 transactions and their disruption by MTM analogues. | |||
Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins.,Hou C, Mandal A, Rohr J, Tsodikov OV Structure. 2021 May 6;29(5):404-412.e4. doi: 10.1016/j.str.2020.11.012. Epub 2020 , Dec 3. PMID:33275876<ref>PMID:33275876</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6vgg" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Core-binding factor|Core-binding factor]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Hou C]] | ||
[[Category: Rohr J]] | |||
[[Category: Tsodikov OV]] | |||