4wpb: Difference between revisions

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-'''Unreleased structure'''
+==Vascular endothelial growth factor in complex with alpha/beta-VEGF-1==
+<StructureSection load='4wpb' size='340' side='right' caption='[[4wpb]], [[Resolution|resolution]] 3.11&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4wpb]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WPB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WPB FirstGlance]. <br>
+</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FB:(3S)-3-AMINO-4-PHENYLBUTANOIC+ACID'>3FB</scene>, <scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=B3D:3-AMINOPENTANEDIOIC+ACID'>B3D</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=XCP:(1S,2S)-2-AMINOCYCLOPENTANECARBOXYLIC+ACID'>XCP</scene>, <scene name='pdbligand=XPC:(3S,4R)-4-AMINOPYRROLIDINE-3-CARBOXYLIC+ACID'>XPC</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=4wpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wpb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wpb RCSB], [http://www.ebi.ac.uk/pdbsum/4wpb PDBsum]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Defects in VEGFA are a cause of susceptibility to microvascular complications of diabetes type 1 (MVCD1) [MIM:[http://omim.org/entry/603933 603933]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
+== Function ==
+[[http://www.uniprot.org/uniprot/VEGFA_HUMAN VEGFA_HUMAN]] Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. NRP1/Neuropilin-1 binds isoforms VEGF-165 and VEGF-145. Isoform VEGF165B binds to KDR but does not activate downstream signaling pathways, does not activate angiogenesis and inhibits tumor growth.<ref>PMID:11427521</ref> <ref>PMID:15520188</ref> <ref>PMID:16489009</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. Here, we describe a strategy for designing oligomers containing both alpha- and beta-amino acid residues ("alpha/beta-peptides") that mimic several peptides derived from the three-helix bundle "Z-domain" scaffold. We show that alpha/beta-peptides derived from a Z-domain peptide targeting vascular endothelial growth factor (VEGF) can structurally and functionally mimic the binding surface of the parent peptide while exhibiting significantly decreased susceptibility to proteolysis. The tightest VEGF-binding alpha/beta-peptide inhibits the VEGF165-induced proliferation of human umbilical vein endothelial cells. We demonstrate the versatility of this strategy by showing how principles underlying VEGF signaling inhibitors can be rapidly extended to produce Z-domain-mimetic alpha/beta-peptides that bind to two other protein partners, IgG and tumor necrosis factor-alpha. Because well-established selection techniques can identify high-affinity Z-domain derivatives from large DNA-encoded libraries, our findings should enable the design of biostable alpha/beta-peptides that bind tightly and specifically to diverse targets of biomedical interest. Such reagents would be useful for diagnostic and therapeutic applications.
-The entry 4wpb is ON HOLD  until Paper Publication
+Targeting diverse protein-protein interaction interfaces with alpha/beta-peptides derived from the Z-domain scaffold.,Checco JW, Kreitler DF, Thomas NC, Belair DG, Rettko NJ, Murphy WL, Forest KT, Gellman SH Proc Natl Acad Sci U S A. 2015 Mar 30. pii: 201420380. PMID:25825775<ref>PMID:25825775</ref>
-Authors: Kreitler, D.F., Checco, J.W., Gellman, S.H., Forest, K.T.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Vascular endothelial growth factor in complex with alpha/beta-VEGF-1
+== References ==
-[[Category: Unreleased Structures]]
+<references/>
-[[Category: Kreitler, D.F]]
+__TOC__
-[[Category: Checco, J.W]]
+</StructureSection>
-[[Category: Forest, K.T]]
+[[Category: Checco, J W]]
-[[Category: Gellman, S.H]]
+[[Category: Forest, K T]]
+[[Category: Gellman, S H]]
+[[Category: Kreitler, D F]]
+[[Category: Alpha/beta-peptide]]
+[[Category: Foldamer]]
+[[Category: Protein binding]]