4y60: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,331,613 edits
No edit summary
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4y60]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y60 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4y60]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y60 FirstGlance]. <br>
</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=4y60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y60 OCA], [https://pdbe.org/4y60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y60 RCSB], [https://www.ebi.ac.uk/pdbsum/4y60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y60 ProSAT]</span></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]] 1.75&#8491;</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=4y60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y60 OCA], [https://pdbe.org/4y60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y60 RCSB], [https://www.ebi.ac.uk/pdbsum/4y60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y60 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/SOX18_MOUSE SOX18_MOUSE] Binds to the consensus sequence 5'-AACAAAG-3' and is able to trans-activate transcription via this site.
[https://www.uniprot.org/uniprot/SOX18_MOUSE SOX18_MOUSE] Binds to the consensus sequence 5'-AACAAAG-3' and is able to trans-activate transcription via this site.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75A presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone. To explore alternatives to challenging small molecule approaches for targeting the DNA-binding activity of SOX18, we designed a set of five decoys based on modified Prox1-DNA. Four decoys potently inhibited DNA binding of SOX18 in vitro and did not interact with non-SOX TFs. Serum stability, nuclease resistance and thermal denaturation assays demonstrated that a decoy circularized with a hexaethylene glycol linker and terminal phosphorothioate modifications is most stable. This SOX decoy also interfered with the expression of a luciferase reporter under control of a SOX18-dependent VCAM1 promoter in COS7 cells. Collectively, we propose SOX decoys as potential strategy for inhibiting SOX18 activity to disrupt tumour-induced neo-lymphangiogenesis.
Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction.,Klaus M, Prokoph N, Girbig M, Wang X, Huang YH, Srivastava Y, Hou L, Narasimhan K, Kolatkar PR, Francois M, Jauch R Nucleic Acids Res. 2016 May 5;44(8):3922-35. doi: 10.1093/nar/gkw130. Epub 2016, Mar 2. PMID:26939885<ref>PMID:26939885</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4y60" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
Retrieved from "https://proteopedia.org/4y60"