2fjh

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[[Image:2fjh.png|left|200px]]
 
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==Structure of the B20-4 Fab, a phage derived Fab fragment, in complex with VEGF==
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The line below this paragraph, containing "STRUCTURE_2fjh", creates the "Structure Box" on the page.
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<StructureSection load='2fjh' size='340' side='right'caption='[[2fjh]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2fjh]] is a 6 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=2FJH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FJH FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fjh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fjh OCA], [https://pdbe.org/2fjh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fjh RCSB], [https://www.ebi.ac.uk/pdbsum/2fjh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fjh ProSAT]</span></td></tr>
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{{STRUCTURE_2fjh| PDB=2fjh | SCENE= }}
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</table>
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== Disease ==
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[https://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:[https://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.
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== Function ==
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[https://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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fj/2fjh_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fjh ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In the quest to discover new research tools and to develop better agents in the fight against cancer, two antibodies, G6 and B20-4, were isolated from synthetic antibody phage libraries. Unlike the AVASTINtrade mark antibody, a recently approved agent for the treatment of patients with colorectal cancer, B20-4 and G6 bind and block both human and murine vascular endothelial growth factor (VEGF). Here we have analyzed and compared the binding epitopes on VEGF for these three antibodies using alanine-scanning mutagenesis and structural analyses. The epitopes recognized by both synthetic antibodies are conserved between human and mouse VEGF, and they match closely to the receptor epitopes both structurally and functionally. In contrast, the Avastin epitope overlaps minimally with the receptor binding surface and centers around a residue that is not conserved in mouse. Our structural and functional analyses elucidate the cross-species reactivity of all three antibodies and emphasize the potential advantages of antibody generation using phage display as the resulting antibodies do not depend on sequence differences across species and preferentially target natural protein-protein interaction surfaces.
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===Structure of the B20-4 Fab, a phage derived Fab fragment, in complex with VEGF===
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Structure-function studies of two synthetic anti-vascular endothelial growth factor Fabs and comparison with the Avastin Fab.,Fuh G, Wu P, Liang WC, Ultsch M, Lee CV, Moffat B, Wiesmann C J Biol Chem. 2006 Mar 10;281(10):6625-31. Epub 2005 Dec 22. PMID:16373345<ref>PMID:16373345</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2fjh" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16373345 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16373345}}
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==About this Structure==
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[[2fjh]] is a 6 chain structure of [[Monoclonal Antibody]] and [[Vascular Endothelial Growth Factor]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FJH OCA].
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==See Also==
==See Also==
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*[[Monoclonal Antibody|Monoclonal Antibody]]
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[Vascular Endothelial Growth Factor|Vascular Endothelial Growth Factor]]
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*[[VEGF 3D Structures|VEGF 3D Structures]]
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*[[3D structures of human antibody|3D structures of human antibody]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:016373345</ref><references group="xtra"/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Wiesmann, C.]]
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[[Category: Large Structures]]
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[[Category: Cystine knot]]
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[[Category: Wiesmann C]]
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[[Category: Fab]]
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[[Category: Hormone-growth factor-immune system complex]]
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[[Category: Protein fab complex]]
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[[Category: Vegf]]
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Current revision

Structure of the B20-4 Fab, a phage derived Fab fragment, in complex with VEGF

PDB ID 2fjh

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