4gs9
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gs9]] is a 2 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=4GS9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GS9 FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gs9]] is a 2 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=4GS9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GS9 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0XB:N-(3-FLUOROPHENYL)-4-NITRO-2,1,3-BENZOXADIAZOL-5-AMINE'>0XB</scene>, <scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0XB:N-(3-FLUOROPHENYL)-4-NITRO-2,1,3-BENZOXADIAZOL-5-AMINE'>0XB</scene>, <scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</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=4gs9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs9 OCA], [https://pdbe.org/4gs9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gs9 RCSB], [https://www.ebi.ac.uk/pdbsum/4gs9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gs9 ProSAT]</span></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=4gs9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gs9 OCA], [https://pdbe.org/4gs9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gs9 RCSB], [https://www.ebi.ac.uk/pdbsum/4gs9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gs9 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/EPAS1_HUMAN EPAS1_HUMAN] Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation seems to require recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD. | [https://www.uniprot.org/uniprot/EPAS1_HUMAN EPAS1_HUMAN] Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation seems to require recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Hypoxia inducible factors (HIFs) are heterodimeric transcription factors induced in a variety of pathophysiological settings, including cancer. We describe the first detailed structure-activity relationship study of small molecules designed to inhibit HIF-2alpha-ARNT heterodimerization by binding an internal cavity of the HIF-2alpha PAS-B domain. Through a series of biophysical characterizations of inhibitor-protein interactions (NMR and X-ray crystallography), we have established the structural requirements for artificial inhibitors of the HIF-2alpha-ARNT PAS-B interaction. These results may serve as a foundation for discovering therapeutic agents that function by a novel mode of action. | ||
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| - | Development of Inhibitors of the PAS-B Domain of the HIF-2alpha Transcription Factor.,Rogers JL, Bayeh L, Scheuermann TH, Longgood J, Key J, Naidoo J, Melito L, Shokri C, Frantz DE, Bruick RK, Gardner KH, Macmillan JB, Tambar UK J Med Chem. 2013 Feb 18. PMID:23363003<ref>PMID:23363003</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gs9" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Crystal structure of the high affinity heterodimer of HIF2 alpha and ARNT C-terminal PAS domains in complex with an inactive benzoxadiazole antagonist
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