3eo1

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{{STRUCTURE_3eo1| PDB=3eo1 | SCENE= }}
 
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===Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3===
 
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{{ABSTRACT_PUBMED_19073914}}
 
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==Disease==
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==Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3==
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[[http://www.uniprot.org/uniprot/TGFB3_HUMAN TGFB3_HUMAN]] Defects in TGFB3 are a cause of familial arrhythmogenic right ventricular dysplasia type 1 (ARVD1) [MIM:[http://omim.org/entry/107970 107970]]; also known as arrhythmogenic right ventricular cardiomyopathy 1 (ARVC1). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.<ref>PMID:15639475</ref>
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<StructureSection load='3eo1' size='340' side='right'caption='[[3eo1]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3eo1]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EO1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EO1 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=3eo1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eo1 OCA], [https://pdbe.org/3eo1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eo1 RCSB], [https://www.ebi.ac.uk/pdbsum/3eo1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eo1 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IGHG4_HUMAN IGHG4_HUMAN]
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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/eo/3eo1_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=3eo1 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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TGF-beta isoforms are key modulators of a broad range of biological pathways and increasingly are exploited as therapeutic targets. Here, we describe the crystal structures of a pan-TGF-beta neutralizing antibody, GC-1008, alone and in complex with TGF-beta3. The antibody is currently in clinical evaluation for idiopathic pulmonary fibrosis, melanoma, and renal cell cancer. GC-1008 recognizes an asymmetric binding interface across the TGF-beta homodimer with high affinity. Whereas both cognate receptors, TGF-beta-receptor types I and II, are required to recognize all 3 TGF-beta isoforms, GC-1008 has been engineered to bind with high affinity to TGF-beta1, 2, and 3 via a single interaction surface. Comparison with existing structures and models of TGF-beta interaction with its receptors suggests that the antibody binds to a similar epitope to the 2 receptors together and is therefore a structurally different but functionally identical mimic of the binding mode of both receptors.
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==Function==
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A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions.,Grutter C, Wilkinson T, Turner R, Podichetty S, Finch D, McCourt M, Loning S, Jermutus L, Grutter MG Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20251-6. Epub 2008 Dec 10. PMID:19073914<ref>PMID:19073914</ref>
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[[http://www.uniprot.org/uniprot/TGFB3_HUMAN TGFB3_HUMAN]] Involved in embryogenesis and cell differentiation.
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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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[[3eo1]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EO1 OCA].
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</div>
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<div class="pdbe-citations 3eo1" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Antibody|Antibody]]
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*[[Antibody 3D structures|Antibody 3D structures]]
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*[[3D structures of non-human antibody|3D structures of non-human antibody]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:019073914</ref><references group="xtra"/><references/>
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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: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Gruetter, C.]]
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[[Category: Gruetter C]]
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[[Category: Gruetter, M G.]]
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[[Category: Gruetter MG]]
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[[Category: Antibody-cytokine complex]]
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[[Category: Cardiomyopathy]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Fab fragment]]
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[[Category: Glycoprotein]]
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[[Category: Growth factor]]
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[[Category: Immune system-cytokine complex]]
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[[Category: Mitogen]]
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[[Category: Secreted]]
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Current revision

Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3

PDB ID 3eo1

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