View source for 4my6


==EnaH-EVH1 in complex with peptidomimetic low-molecular weight inhibitor Ac-[2-Cl-F]-[ProM-2]-[ProM-1]-OH==
<StructureSection load='4my6' size='340' side='right'caption='[[4my6]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4my6]] 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=4MY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MY6 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3VH:(3aR,5aS,8S,10aS)-1-[(3S,6R,8aS)-1-[(2S)-2-acetamido-3-(2-chlorophenyl)propanoyl]-5-oxidanylidene-spiro[1,2,3,8a-tetrahydroindolizine-6,2-pyrrolidine]-3-yl]carbonyl-10-oxidanylidene-2,3,3a,5a,8,10a-hexahydrodipyrrolo[3,2-b 3,1-f]azepine-8-carboxylic+acid'>3VH</scene>, <scene name='pdbligand=BR:BROMIDE+ION'>BR</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=4my6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4my6 OCA], [https://pdbe.org/4my6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4my6 RCSB], [https://www.ebi.ac.uk/pdbsum/4my6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4my6 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ENAH_HUMAN ENAH_HUMAN] Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells. ENAH induces the formation of F-actin rich outgrowths in fibroblasts. Acts synergistically with BAIAP2-alpha and downstream of NTN1 to promote filipodia formation (By similarity).<ref>PMID:11696321</ref> <ref>PMID:18158903</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Small-molecule competitors of protein-protein interactions are urgently needed for functional analysis of large-scale genomics and proteomics data. Particularly abundant, yet so far undruggable, targets include domains specialized in recognizing proline-rich segments, including Src-homology 3 (SH3), WW, GYF, and Drosophila enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. Here, we present a modular strategy to obtain an extendable toolkit of chemical fragments (ProMs) designed to replace pairs of conserved prolines in recognition motifs. As proof-of-principle, we developed a small, selective, peptidomimetic inhibitor of Ena/VASP EVH1 domain interactions. Highly invasive MDA MB 231 breast-cancer cells treated with this ligand showed displacement of VASP from focal adhesions, as well as from the front of lamellipodia, and strongly reduced cell invasion. General applicability of our strategy is illustrated by the design of an ErbB4-derived ligand containing two ProM-1 fragments, targeting the yes-associated protein 1 (YAP1)-WW domain with a fivefold higher affinity.

A modular toolkit to inhibit proline-rich motif-mediated protein-protein interactions.,Opitz R, Muller M, Reuter C, Barone M, Soicke A, Roske Y, Piotukh K, Huy P, Beerbaum M, Wiesner B, Beyermann M, Schmieder P, Freund C, Volkmer R, Oschkinat H, Schmalz HG, Kuhne R Proc Natl Acad Sci U S A. 2015 Apr 6. pii: 201422054. PMID:25848013<ref>PMID:25848013</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4my6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Barone M]]
[[Category: Kuehne R]]
[[Category: Roske Y]]