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3giz

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Crystal structure of the Fab fragment of anti-CD20 antibody Ofatumumab

Structural highlights

3giz is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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^[1]

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

References

↑ Du J, Yang H, Guo Y, Ding J. Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20. Mol Immunol. 2009 Jul;46(11-12):2419-23. Epub 2009 May 8. PMID:19427037 doi:10.1016/j.molimm.2009.04.009

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3giz"

Categories: Homo sapiens | Large Structures | Ding J | Du J | Yang H

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=3GIZ FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3giz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3giz OCA], [http://pdbe.org/3giz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3giz RCSB], [http://www.ebi.ac.uk/pdbsum/3giz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3giz ProSAT]</span></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 ==
@@ Line 29: / Line 30: @@
 ==See Also==
 *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
-*[[Ofatumumab|Ofatumumab]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ding, J]]
+[[Category: Ding J]]
-[[Category: Du, J]]
+[[Category: Du J]]
-[[Category: Yang, H]]
+[[Category: Yang H]]
-[[Category: Antibody]]
-[[Category: Cd20]]
-[[Category: Fab]]
-[[Category: Fully human antibody]]
-[[Category: Hu-maxcd20]]
-[[Category: Immune system]]
-[[Category: Ofatumumab]]

3giz

From Proteopedia

Current revision

Crystal structure of the Fab fragment of anti-CD20 antibody Ofatumumab

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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