3bdy

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{{STRUCTURE_3bdy| PDB=3bdy | SCENE= }}
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==Dual specific bH1 Fab in complex with VEGF==
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===Dual specific bH1 Fab in complex with VEGF===
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<StructureSection load='3bdy' size='340' side='right' caption='[[3bdy]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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{{ABSTRACT_PUBMED_19299620}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3bdy]] is a 3 chain structure 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3BDY FirstGlance]. <br>
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==Disease==
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3be1|3be1]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VEGF, VEGFA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bdy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bdy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3bdy RCSB], [http://www.ebi.ac.uk/pdbsum/3bdy PDBsum]</span></td></tr>
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<table>
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== 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.
[[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.
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== Function ==
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[[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>
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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/chain_selection.php?pdb_ID=2ata 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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==Function==
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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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[[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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3bdy]] is a 3 chain structure 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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</div>
==See Also==
==See Also==
*[[Antibody|Antibody]]
*[[Antibody|Antibody]]
*[[Vascular Endothelial Growth Factor|Vascular Endothelial Growth Factor]]
*[[Vascular Endothelial Growth Factor|Vascular Endothelial Growth Factor]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:019299620</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Appleton, B A.]]
[[Category: Appleton, B A.]]

Revision as of 21:39, 2 October 2014

Dual specific bH1 Fab in complex with VEGF

3bdy, resolution 2.60Å

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