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5nc7

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Revision as of 07:03, 25 November 2020

ENAH EVH1 in complex with Ac-WPPPPTEDEL-NH2

Structural highlights

5nc7 is a 12 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	,
Gene:	ENAH, MENA (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Krugmann S, Jordens I, Gevaert K, Driessens M, Vandekerckhove J, Hall A. Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Curr Biol. 2001 Oct 30;11(21):1645-55. PMID:11696321
↑ Boeda B, Briggs DC, Higgins T, Garvalov BK, Fadden AJ, McDonald NQ, Way M. Tes, a specific Mena interacting partner, breaks the rules for EVH1 binding. Mol Cell. 2007 Dec 28;28(6):1071-82. PMID:18158903 doi:10.1016/j.molcel.2007.10.033
↑ 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. A modular toolkit to inhibit proline-rich motif-mediated protein-protein interactions. Proc Natl Acad Sci U S A. 2015 Apr 6. pii: 201422054. PMID:25848013 doi:http://dx.doi.org/10.1073/pnas.1422054112

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5nc7"

@@ Line 3: / Line 3: @@
 <StructureSection load='5nc7' size='340' side='right'caption='[[5nc7]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5nc7]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NC7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NC7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5nc7]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NC7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NC7 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ENAH, MENA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5nc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nc7 OCA], [http://pdbe.org/5nc7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nc7 RCSB], [http://www.ebi.ac.uk/pdbsum/5nc7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nc7 ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Barone, M]]

5nc7

From Proteopedia

Revision as of 07:03, 25 November 2020

ENAH EVH1 in complex with Ac-WPPPPTEDEL-NH2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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