View source for 3giz


==Crystal structure of the Fab fragment of anti-CD20 antibody Ofatumumab==
<StructureSection load='3giz' size='340' side='right'caption='[[3giz]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3giz]] is a 2 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=3GIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GIZ 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3giz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3giz OCA], [https://pdbe.org/3giz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3giz RCSB], [https://www.ebi.ac.uk/pdbsum/3giz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3giz 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/gi/3giz_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=3giz ConSurf].
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== Publication Abstract from PubMed ==
CD20 is an important drug target for B-cell depletion therapy against certain B-cell lymphomas and autoimmune diseases. The success of anti-CD20 antibody drugs such as Rituximab, Ibritumomab, and Tositumomab has promoted the development of new generation of anti-CD20 antibodies for therapeutic applications. Ofatumumab is a fully human anti-CD20 antibody that is currently in phase III clinical trial for several types of malignancies and autoimmune diseases and is one of the most promising anti-CD20 drugs. Here we report the crystal structure of the Fab fragment of Ofatumumab at 2.2A resolution. The antigen combining site is composed of a large, deep pocket formed by six CDR loops. The pocket has a hydrophobic periphery and a positively charged bottom. Structure analysis and comparison with other antibodies suggest that the hydrophobic periphery might interact with the epitope on CD20 that is enriched with hydrophobic residues and very close to cell membrane, and the positively charged bottom might interact with Glu(150) of CD20 which is the only negatively charged residue within the epitope. These results provide some insights into the recognition of Ofatumumab with CD20 and explain how the antibody can recognize an epitope so close to the cell membrane.

Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20.,Du J, Yang H, Guo Y, Ding J Mol Immunol. 2009 Jul;46(11-12):2419-23. Epub 2009 May 8. PMID:19427037<ref>PMID:19427037</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding J]]
[[Category: Du J]]
[[Category: Yang H]]