2fjf: Difference between revisions

New page: left|200px<br /> <applet load="2fjf" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fjf, resolution 2.65Å" /> '''Structure of the G6...
 
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[[Image:2fjf.gif|left|200px]]<br />
<applet load="2fjf" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2fjf, resolution 2.65&Aring;" />
'''Structure of the G6 Fab, a phage derived VEGF binding Fab'''<br />


==Overview==
==Structure of the G6 Fab, a phage derived VEGF binding Fab==
In the quest to discover new research tools and to develop better agents, in the fight against cancer, two antibodies, G6 and B20-4, were isolated, from synthetic antibody phage libraries. Unlike the AVASTINtrade mark, antibody, a recently approved agent for the treatment of patients with, colorectal cancer, B20-4 and G6 bind and block both human and murine, vascular endothelial growth factor (VEGF). Here we have analyzed and, compared the binding epitopes on VEGF for these three antibodies using, alanine-scanning mutagenesis and structural analyses. The epitopes, recognized by both synthetic antibodies are conserved between human and, mouse VEGF, and they match closely to the receptor epitopes both, structurally and functionally. In contrast, the Avastin epitope overlaps, minimally with the receptor binding surface and centers around a residue, that is not conserved in mouse. Our structural and functional analyses, elucidate the cross-species reactivity of all three antibodies and, emphasize the potential advantages of antibody generation using phage, display as the resulting antibodies do not depend on sequence differences, across species and preferentially target natural protein-protein, interaction surfaces.
<StructureSection load='2fjf' size='340' side='right'caption='[[2fjf]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2fjf]] 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=2FJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FJF FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65&#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=2fjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fjf OCA], [https://pdbe.org/2fjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fjf RCSB], [https://www.ebi.ac.uk/pdbsum/2fjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fjf ProSAT]</span></td></tr>
</table>
== 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/fj/2fjf_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=2fjf ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
In the quest to discover new research tools and to develop better agents in the fight against cancer, two antibodies, G6 and B20-4, were isolated from synthetic antibody phage libraries. Unlike the AVASTINtrade mark antibody, a recently approved agent for the treatment of patients with colorectal cancer, B20-4 and G6 bind and block both human and murine vascular endothelial growth factor (VEGF). Here we have analyzed and compared the binding epitopes on VEGF for these three antibodies using alanine-scanning mutagenesis and structural analyses. The epitopes recognized by both synthetic antibodies are conserved between human and mouse VEGF, and they match closely to the receptor epitopes both structurally and functionally. In contrast, the Avastin epitope overlaps minimally with the receptor binding surface and centers around a residue that is not conserved in mouse. Our structural and functional analyses elucidate the cross-species reactivity of all three antibodies and emphasize the potential advantages of antibody generation using phage display as the resulting antibodies do not depend on sequence differences across species and preferentially target natural protein-protein interaction surfaces.


==Disease==
Structure-function studies of two synthetic anti-vascular endothelial growth factor Fabs and comparison with the Avastin Fab.,Fuh G, Wu P, Liang WC, Ultsch M, Lee CV, Moffat B, Wiesmann C J Biol Chem. 2006 Mar 10;281(10):6625-31. Epub 2005 Dec 22. PMID:16373345<ref>PMID:16373345</ref>
Known disease associated with this structure: Kappa light chain deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147200 147200]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2FJF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FJF OCA].
</div>
<div class="pdbe-citations 2fjf" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structure-function studies of two synthetic anti-vascular endothelial growth factor Fabs and comparison with the Avastin Fab., Fuh G, Wu P, Liang WC, Ultsch M, Lee CV, Moffat B, Wiesmann C, J Biol Chem. 2006 Mar 10;281(10):6625-31. Epub 2005 Dec 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16373345 16373345]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Wiesmann, C.]]
[[Category: Wiesmann C]]
[[Category: antibody]]
[[Category: dodecamer]]
[[Category: fab]]
 
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