2qr0

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{{Seed}}
 
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[[Image:2qr0.png|left|200px]]
 
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==Structure of VEGF complexed to a Fab containing TYR and SER in the CDRs==
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The line below this paragraph, containing "STRUCTURE_2qr0", creates the "Structure Box" on the page.
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<StructureSection load='2qr0' size='340' side='right'caption='[[2qr0]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[2qr0]] is a 24 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=2QR0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QR0 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 3.5&#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=2qr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qr0 OCA], [https://pdbe.org/2qr0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qr0 RCSB], [https://www.ebi.ac.uk/pdbsum/2qr0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qr0 ProSAT]</span></td></tr>
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{{STRUCTURE_2qr0| PDB=2qr0 | 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/qr/2qr0_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2qr0 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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We have previously established a minimalist approach to antibody engineering by using a phage-displayed framework to support complementarity determining region (CDR) diversity restricted to a binary code of tyrosine and serine. Here, we systematically augmented the original binary library with additional levels of diversity and examined the effects. The diversity of the simplest library, in which only heavy chain CDR positions were randomized by the binary code, was expanded in a stepwise manner by adding diversity to the light chain, by diversifying non-paratope residues that may influence CDR conformations, and by adding additional chemical diversity to CDR-H3. The additional diversity incrementally improved the affinities of antibodies raised against human vascular endoethelial growth factor and the structure of an antibody-antigen complex showed that tyrosine side-chains are sufficient to mediate most of the interactions with antigen, but a glycine residue in CDR-H3 was critical for providing a conformation suitable for high-affinity binding. Using new high-throughput procedures and the most complex library, we produced multiple high-affinity antibodies with dissociation constants in the single-digit nanomolar range against a wide variety of protein antigens. Thus, this fully synthetic, minimalist library has essentially recapitulated the capacity of the natural immune system to generate high-affinity antibodies. Libraries of this type should be highly useful for proteomic applications, as they minimize inherent complexities of natural antibodies that have hindered the establishment of high-throughput procedures. Furthermore, analysis of a large number of antibodies derived from these well-defined and simplistic libraries allowed us to uncover statistically significant trends in CDR sequences, which provide valuable insights into antibody library design and into factors governing protein-protein interactions.
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===Structure of VEGF complexed to a Fab containing TYR and SER in the CDRs===
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High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries.,Fellouse FA, Esaki K, Birtalan S, Raptis D, Cancasci VJ, Koide A, Jhurani P, Vasser M, Wiesmann C, Kossiakoff AA, Koide S, Sidhu SS J Mol Biol. 2007 Nov 2;373(4):924-40. Epub 2007 Aug 19. PMID:17825836<ref>PMID:17825836</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>
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<div class="pdbe-citations 2qr0" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17825836}}, adds the Publication Abstract to the page
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*[[Antibody 3D structures|Antibody 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17825836 is the PubMed ID number.
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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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{{ABSTRACT_PUBMED_17825836}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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2QR0 is a [[Single protein]] structure of 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=2QR0 OCA].
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</StructureSection>
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==Reference==
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High-throughput generation of synthetic antibodies from highly functional minimalist phage-displayed libraries., Fellouse FA, Esaki K, Birtalan S, Raptis D, Cancasci VJ, Koide A, Jhurani P, Vasser M, Wiesmann C, Kossiakoff AA, Koide S, Sidhu SS, J Mol Biol. 2007 Nov 2;373(4):924-40. Epub 2007 Aug 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17825836 17825836]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Wiesmann, C.]]
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[[Category: Wiesmann C]]
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[[Category: Antibody recognition]]
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[[Category: Immune system]]
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[[Category: Phage display]]
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[[Category: Specificity]]
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[[Category: Vegf]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:37:25 2008''
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Current revision

Structure of VEGF complexed to a Fab containing TYR and SER in the CDRs

PDB ID 2qr0

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