View source for 6i10


==CRYSTAL STRUCTURE OF FASCIN IN COMPLEX WITH COMPOUND 2==
<StructureSection load='6i10' size='340' side='right'caption='[[6i10]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6i10]] is a 1 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=6I10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I10 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GZK:1-[(3~{R})-1,1-bis(oxidanylidene)thiolan-3-yl]-5-[(3,4-dichlorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one'>GZK</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=6i10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i10 OCA], [https://pdbe.org/6i10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i10 RCSB], [https://www.ebi.ac.uk/pdbsum/6i10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i10 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FSCN1_HUMAN FSCN1_HUMAN] Organizes filamentous actin into bundles with a minimum of 4.1:1 actin/fascin ratio. Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers. Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration.<ref>PMID:9362073</ref> <ref>PMID:9571235</ref> <ref>PMID:20137952</ref> <ref>PMID:20393565</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fascin is an actin binding and bundling protein that is not expressed in normal epithelial tissues but overexpressed in a variety of invasive epithelial tumors. It has a critical role in cancer cell metastasis by promoting cell migration and invasion. Here we report the crystal structures of fascin in complex with a series of novel and potent inhibitors. Structure-based elaboration of these compounds enabled the development of a series with nanomolar affinities for fascin, good physicochemical properties and the ability to inhibit fascin-mediated bundling of filamentous actin. These compounds provide promising starting points for fascin-targeted anti-metastatic therapies.

Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents.,Francis S, Croft D, Schuttelkopf AW, Parry C, Pugliese A, Cameron K, Claydon S, Drysdale M, Gardner C, Gohlke A, Goodwin G, Gray CH, Konczal J, McDonald L, Mezna M, Pannifer A, Paul NR, Machesky L, McKinnon H, Bower J Bioorg Med Chem Lett. 2019 Jan 30. pii: S0960-894X(19)30056-3. doi:, 10.1016/j.bmcl.2019.01.035. PMID:30773430<ref>PMID:30773430</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6i10" style="background-color:#fffaf0;"></div>

==See Also==
*[[Fascin|Fascin]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Schuettelkopf AW]]