5nd0 - Revision history

OCA at 09:51, 15 November 2023

OCA — Wed, 15 Nov 2023 09:51:43 GMT

←Older revision		Revision as of 09:51, 15 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5nd0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5nd0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:(3~{S},7~{R},10~{R},13~{S})-2-oxidanylidene-1,4-diazatricyclo[8.3.0.0^{3,7}]tridec-8-ene-13-carbaldehyde'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.45Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:(3~{S},7~{R},10~{R},13~{S})-2-oxidanylidene-1,4-diazatricyclo[8.3.0.0^{3,7}]tridec-8-ene-13-carbaldehyde'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [https://pdbe.org/5nd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [https://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></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=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [https://pdbe.org/5nd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [https://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:15, 26 October 2022

OCA — Wed, 26 Oct 2022 06:15:55 GMT

←Older revision		Revision as of 06:15, 26 October 2022
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	<StructureSection load='5nd0' size='340' side='right'caption='[[5nd0]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='5nd0' size='340' side='right'caption='[[5nd0]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nd0]] is a 4 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=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nd0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat~~"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:(3~{S},7~{R},10~{R},13~{S})-2-oxidanylidene-1,4-diazatricyclo[8.3.0.0^{3,7}]tridec-8-ene-13-carbaldehyde'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat~~"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</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=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [https://pdbe.org/5nd0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [https://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></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=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [~~http~~://pdbe.org/5nd0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://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>	+	[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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== 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~~.	+	Battling metastasis through inhibition of cell motility is considered a promising approach to support cancer therapies. In this context, Ena/VASP-depending signaling pathways, in particular interactions with their EVH1 domains, are promising targets for pharmaceutical intervention. However, protein-protein interactions involving proline-rich segments are notoriously difficult to address by small molecules. Hence, structure-based design efforts in combination with the chemical synthesis of additional molecular entities are required. Building on a previously developed nonpeptidic micromolar inhibitor, we determined 22 crystal structures of ENAH EVH1 in complex with inhibitors and rationally extended our library of conformationally defined proline-derived modules (ProMs) to succeed in developing a nanomolar inhibitor ([Formula: see text] Da). In contrast to the previous inhibitor, the optimized compounds reduced extravasation of invasive breast cancer cells in a zebrafish model. This study represents an example of successful, structure-guided development of low molecular weight inhibitors specifically and selectively addressing a proline-rich sequence-recognizing domain that is characterized by a shallow epitope lacking defined binding pockets. The evolved high-affinity inhibitor may now serve as a tool in validating the basic therapeutic concept, i.e., the suppression of cancer metastasis by inhibiting a crucial protein-protein interaction involved in actin filament processing and cell migration.

-	~~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>	+	Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells.,Barone M, Muller M, Chiha S, Ren J, Albat D, Soicke A, Dohmen S, Klein M, Bruns J, van Dinther M, Opitz R, Lindemann P, Beerbaum M, Motzny K, Roske Y, Schmieder P, Volkmer R, Nazare M, Heinemann U, Oschkinat H, Ten Dijke P, Schmalz HG, Kuhne R Proc Natl Acad Sci U S A. 2020 Nov 12. pii: 2007213117. doi:, 10.1073/pnas.2007213117. PMID:33184177<ref>PMID:33184177</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Barone, M~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Roske, Y~~]]	+	[[Category: Barone M]]
-	[[Category: ~~Acta]]~~	+	[[Category: Roske Y]]
-	~~[[Category: Cell adhesion]]~~	+
-	~~[[Category: Proline-rich motif]]~~	+
-	~~[[Category: Protein-protein interaction~~]]	+

OCA at 07:03, 25 November 2020

OCA — Wed, 25 Nov 2020 07:03:57 GMT

←Older revision		Revision as of 07:03, 25 November 2020
Line 3:		Line 3:
	<StructureSection load='5nd0' size='340' side='right'caption='[[5nd0]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='5nd0' size='340' side='right'caption='[[5nd0]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nd0]] is a 4 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=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nd0]] is a 4 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=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</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='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://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [http://pdbe.org/5nd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [http://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></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=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [http://pdbe.org/5nd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [http://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 17:11, 14 August 2019

OCA — Wed, 14 Aug 2019 17:11:01 GMT

←Older revision		Revision as of 17:11, 14 August 2019
Line 1:		Line 1:

	==ENAH EVH1 in complex with Ac-[2-Cl-F]-PP-[ProM-1]-TEDEL-NH2==		==ENAH EVH1 in complex with Ac-[2-Cl-F]-PP-[ProM-1]-TEDEL-NH2==
-	<StructureSection load='5nd0' size='340' side='right' caption='[[5nd0]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='5nd0' size='340' side='right'caption='[[5nd0]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nd0]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nd0]] is a 4 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=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [http://pdbe.org/5nd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [http://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [http://pdbe.org/5nd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [http://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></td></tr>
	</table>		</table>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Barone, M]]		[[Category: Barone, M]]
	[[Category: Roske, Y]]		[[Category: Roske, Y]]

OCA at 07:30, 21 March 2018

OCA — Wed, 21 Mar 2018 07:30:19 GMT

←Older revision		Revision as of 07:30, 21 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5nd0 is ~~ON HOLD~~	+	==ENAH EVH1 in complex with Ac-[2-Cl-F]-PP-[ProM-1]-TEDEL-NH2==
		+	<StructureSection load='5nd0' size='340' side='right' caption='[[5nd0]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5nd0]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ND0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ND0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=2L5:2-CHLORO-L-PHENYLALANINE'>2L5</scene>, <scene name='pdbligand=8TQ:'>8TQ</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NLW:L-LEUCINAMIDE'>NLW</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nd0 OCA], [http://pdbe.org/5nd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nd0 RCSB], [http://www.ebi.ac.uk/pdbsum/5nd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nd0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://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.

-	~~Authors: Barone~~, M., ~~Roske~~, Y.	+	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>

-	~~Description: ENAH EVH1 in complex with Ac~~-[2-~~Cl-F]-PP-[ProM-1]-TEDEL-NH2~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	~~[[Category: Roske, Y]]~~	+	<div class="pdbe-citations 5nd0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Barone, M]]		[[Category: Barone, M]]
		+	[[Category: Roske, Y]]
		+	[[Category: Acta]]
		+	[[Category: Cell adhesion]]
		+	[[Category: Proline-rich motif]]
		+	[[Category: Protein-protein interaction]]

OCA: Protected "5nd0" [edit=sysop:move=sysop]

OCA — Wed, 15 Mar 2017 17:25:56 GMT

Protected "5nd0" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:25, 15 March 2017

OCA: New page: '''Unreleased structure''' The entry 5nd0 is ON HOLD Authors: Barone, M., Roske, Y. Description: ENAH EVH1 in complex with Ac-[2-Cl-F]-PP-[ProM-1]-TEDEL-NH2 [[Category: Unreleased Stru...

OCA — Wed, 15 Mar 2017 17:25:55 GMT

New page: '''Unreleased structure''' The entry 5nd0 is ON HOLD Authors: Barone, M., Roske, Y. Description: ENAH EVH1 in complex with Ac-[2-Cl-F]-PP-[ProM-1]-TEDEL-NH2 [[Category: Unreleased Stru...

New page

'''Unreleased structure'''

The entry 5nd0 is ON HOLD

Authors: Barone, M., Roske, Y.

Description: ENAH EVH1 in complex with Ac-[2-Cl-F]-PP-[ProM-1]-TEDEL-NH2
[[Category: Unreleased Structures]]
[[Category: Roske, Y]]
[[Category: Barone, M]]