3eo1: Difference between revisions

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{{Seed}}
[[Image:3eo1.png|left|200px]]


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==Structure of the Fab Fragment of GC-1008 in Complex with Transforming Growth Factor-Beta 3==
The line below this paragraph, containing "STRUCTURE_3eo1", creates the "Structure Box" on the page.
<StructureSection load='3eo1' size='340' side='right'caption='[[3eo1]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</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>
-->
<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>
{{STRUCTURE_3eo1|  PDB=3eo1  |  SCENE=  }}
</table>
== Function ==
[https://www.uniprot.org/uniprot/IGHG4_HUMAN IGHG4_HUMAN]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eo/3eo1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


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


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3eo1" style="background-color:#fffaf0;"></div>


==Disease==
==See Also==
Known disease associated with this structure: Arrhythmogenic right ventricular dysplasia 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190230 190230]]
*[[Antibody 3D structures|Antibody 3D structures]]
 
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
==About this Structure==
== References ==
3EO1 is a 12 chains structure of sequences 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].
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Gruetter, C.]]
[[Category: Gruetter C]]
[[Category: Gruetter, M G.]]
[[Category: Gruetter MG]]
[[Category: Antibody-cytokine complex]]
[[Category: Cardiomyopathy]]
[[Category: Cleavage on pair of basic residue]]
[[Category: Fab fragment]]
[[Category: Glycoprotein]]
[[Category: Growth factor]]
[[Category: Immune system/cytokine complex]]
[[Category: Mitogen]]
[[Category: Polymorphism]]
[[Category: Secreted]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 10 15:40:46 2008''

Latest revision as of 10:56, 9 October 2024

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

Structural highlights

3eo1 is a 12 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.1Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IGHG4_HUMAN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Grutter C, Wilkinson T, Turner R, Podichetty S, Finch D, McCourt M, Loning S, Jermutus L, Grutter MG. A cytokine-neutralizing antibody as a structural mimetic of 2 receptor interactions. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20251-6. Epub 2008 Dec 10. PMID:19073914 doi:0807200106

3eo1, resolution 3.10Å

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