4y60

</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>

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== 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>

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== References ==

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