3bdy

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[[Image:3bdy.png|left|200px]]
 
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==Dual specific bH1 Fab in complex with VEGF==
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The line below this paragraph, containing "STRUCTURE_3bdy", creates the "Structure Box" on the page.
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<StructureSection load='3bdy' size='340' side='right'caption='[[3bdy]], [[Resolution|resolution]] 2.60&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'>[[3bdy]] is a 3 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=3BDY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BDY 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]] 2.6&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
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{{STRUCTURE_3bdy| PDB=3bdy | SCENE= }}
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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=3bdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bdy OCA], [https://pdbe.org/3bdy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bdy RCSB], [https://www.ebi.ac.uk/pdbsum/3bdy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bdy ProSAT]</span></td></tr>
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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/bd/3bdy_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=3bdy 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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The interface between antibody and antigen is often depicted as a lock and key, suggesting that an antibody surface can accommodate only one antigen. Here, we describe an antibody with an antigen binding site that binds two distinct proteins with high affinity. We isolated a variant of Herceptin, a therapeutic monoclonal antibody that binds the human epidermal growth factor receptor 2 (HER2), on the basis of its ability to simultaneously interact with vascular endothelial growth factor (VEGF). Crystallographic and mutagenesis studies revealed that distinct amino acids of this antibody, called bH1, engage HER2 and VEGF energetically, but there is extensive overlap between the antibody surface areas contacting the two antigens. An affinity-improved version of bH1 inhibits both HER2- and VEGF-mediated cell proliferation in vitro and tumor progression in mouse models. Such "two-in-one" antibodies challenge the monoclonal antibody paradigm of one binding site, one antigen. They could also provide new opportunities for antibody-based therapy.
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===Dual specific bH1 Fab in complex with VEGF===
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Variants of the antibody herceptin that interact with HER2 and VEGF at the antigen binding site.,Bostrom J, Yu SF, Kan D, Appleton BA, Lee CV, Billeci K, Man W, Peale F, Ross S, Wiesmann C, Fuh G Science. 2009 Mar 20;323(5921):1610-4. PMID:19299620<ref>PMID:19299620</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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The line below this paragraph, {{ABSTRACT_PUBMED_19299620}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 3bdy" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 19299620 is the PubMed ID number.
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{{ABSTRACT_PUBMED_19299620}}
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==About this Structure==
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[[3bdy]] is a 3 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=3BDY 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:019299620</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: Appleton, B A.]]
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[[Category: Large Structures]]
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[[Category: Bostrom, J M.]]
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[[Category: Appleton BA]]
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[[Category: Wiesmann, C.]]
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[[Category: Bostrom JM]]
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[[Category: Angiogenesis]]
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[[Category: Wiesmann C]]
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[[Category: Developmental protein]]
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[[Category: Differentiation]]
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[[Category: Fab complex]]
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[[Category: Glycoprotein]]
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[[Category: Growth factor]]
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[[Category: Heparin-binding]]
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[[Category: Hormone]]
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[[Category: Mitogen]]
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[[Category: Secreted]]
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Current revision

Dual specific bH1 Fab in complex with VEGF

PDB ID 3bdy

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