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[[Image:2osl.gif|left|200px]]
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{{STRUCTURE_2osl|  PDB=2osl  |  SCENE=  }}
'''Crystal structure of Rituximab Fab in complex with an epitope peptide'''


==Crystal structure of Rituximab Fab in complex with an epitope peptide==
<StructureSection load='2osl' size='340' side='right'caption='[[2osl]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2osl]] is a 6 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=2OSL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OSL 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]] 2.6&#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=2osl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2osl OCA], [https://pdbe.org/2osl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2osl RCSB], [https://www.ebi.ac.uk/pdbsum/2osl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2osl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN] Defects in MS4A1 are the cause of immunodeficiency common variable type 5 (CVID5) [MIM:[https://omim.org/entry/613495 613495]; also called antibody deficiency due to CD20 defect. CVID5 is a primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low.<ref>PMID:20038800</ref>
== Function ==
[https://www.uniprot.org/uniprot/CD20_HUMAN CD20_HUMAN] This protein may be involved in the regulation of B-cell activation and proliferation.
== 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/os/2osl_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=2osl ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Rituximab is a widely used monoclonal antibody drug for treating certain lymphomas and autoimmune diseases. To understand the molecular mechanism of recognition of human CD20 by Rituximab, we determined the crystal structure of the Rituximab Fab in complex with a synthesized peptide comprising the CD20 epitope (residues 163-187) at 2.6-A resolution. The combining site of the Fab consists of four complementarity determining regions that form a large, deep pocket to accommodate the epitope peptide. The bound peptide assumes a unique cyclic conformation that is constrained by a disulfide bond and a rigid proline residue (Pro(172)). The (170)ANPS(173) motif of CD20 is deeply embedded into the pocket on the antibody surface and plays an essential role in the recognition and binding of Rituximab. The antigen-antibody interactions involve both hydrogen bonds and van der Waals contacts and display a high degree of structural and chemical complementarity. These results provide a molecular basis for the specific recognition of CD20 by Rituximab as well as valuable information for development of improved antibody drugs with better specificity and higher affinity.


==Overview==
Structural basis for recognition of CD20 by therapeutic antibody Rituximab.,Du J, Wang H, Zhong C, Peng B, Zhang M, Li B, Huo S, Guo Y, Ding J J Biol Chem. 2007 May 18;282(20):15073-80. Epub 2007 Mar 29. PMID:17395584<ref>PMID:17395584</ref>
Rituximab is a widely used monoclonal antibody drug for treating certain lymphomas and autoimmune diseases. To understand the molecular mechanism of recognition of human CD20 by Rituximab, we determined the crystal structure of the Rituximab Fab in complex with a synthesized peptide comprising the CD20 epitope (residues 163-187) at 2.6-A resolution. The combining site of the Fab consists of four complementarity determining regions that form a large, deep pocket to accommodate the epitope peptide. The bound peptide assumes a unique cyclic conformation that is constrained by a disulfide bond and a rigid proline residue (Pro(172)). The (170)ANPS(173) motif of CD20 is deeply embedded into the pocket on the antibody surface and plays an essential role in the recognition and binding of Rituximab. The antigen-antibody interactions involve both hydrogen bonds and van der Waals contacts and display a high degree of structural and chemical complementarity. These results provide a molecular basis for the specific recognition of CD20 by Rituximab as well as valuable information for development of improved antibody drugs with better specificity and higher affinity.


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


==Reference==
==See Also==
Structural basis for recognition of CD20 by therapeutic antibody Rituximab., Du J, Wang H, Zhong C, Peng B, Zhang M, Li B, Huo S, Guo Y, Ding J, J Biol Chem. 2007 May 18;282(20):15073-80. Epub 2007 Mar 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17395584 17395584]
*[[Antibody|Antibody]]
[[Category: Homo sapiens, mus musculus]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
[[Category: Single protein]]
*[[Monoclonal Antibody|Monoclonal Antibody]]
[[Category: Ding, J.]]
== References ==
[[Category: Du, J.]]
<references/>
[[Category: Zhong, C.]]
__TOC__
[[Category: Chimeric antibody]]
</StructureSection>
[[Category: Fab-peptide complex]]
[[Category: Homo sapiens]]
[[Category: Rituximab]]
[[Category: Large Structures]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 11:34:28 2008''
[[Category: Mus musculus]]
[[Category: Ding J]]
[[Category: Du J]]
[[Category: Zhong C]]
Retrieved from "https://proteopedia.org/2osl"