2xa8: Difference between revisions
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== | ==Crystal structure of the Fab domain of omalizumab at 2.41A== | ||
<StructureSection load='2xa8' size='340' side='right' caption='[[2xa8]], [[Resolution|resolution]] 2.42Å' scene=''> | <StructureSection load='2xa8' size='340' side='right' caption='[[2xa8]], [[Resolution|resolution]] 2.42Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2xa8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XA8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XA8 FirstGlance]. <br> | <table><tr><td colspan='2'>[[2xa8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XA8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XA8 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xa8 RCSB], [http://www.ebi.ac.uk/pdbsum/2xa8 PDBsum]</span></td></tr> | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xa8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa8 OCA], [http://pdbe.org/2xa8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xa8 RCSB], [http://www.ebi.ac.uk/pdbsum/2xa8 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcepsilonRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcepsilonRI and omalizumab-binding sites in the Cepsilon3 domain, but crystallographic studies show FcepsilonRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-A omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcepsilonRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcepsilonRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcepsilonRI. | |||
Structural and Physical Basis for Anti-IgE Therapy.,Wright JD, Chu HM, Huang CH, Ma C, Chang TW, Lim C Sci Rep. 2015 Jun 26;5:11581. doi: 10.1038/srep11581. PMID:26113483<ref>PMID:26113483</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2xa8" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 21:29, 27 January 2016
Crystal structure of the Fab domain of omalizumab at 2.41ACrystal structure of the Fab domain of omalizumab at 2.41A
Structural highlights
Publication Abstract from PubMedOmalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcepsilonRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcepsilonRI and omalizumab-binding sites in the Cepsilon3 domain, but crystallographic studies show FcepsilonRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-A omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcepsilonRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcepsilonRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcepsilonRI. Structural and Physical Basis for Anti-IgE Therapy.,Wright JD, Chu HM, Huang CH, Ma C, Chang TW, Lim C Sci Rep. 2015 Jun 26;5:11581. doi: 10.1038/srep11581. PMID:26113483[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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