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4xxd

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'''Unreleased structure'''
 
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The entry 4xxd is ON HOLD
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==Crystal Structure of mid-region amyloid beta capture by solanezumab==
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<StructureSection load='4xxd' size='340' side='right'caption='[[4xxd]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4xxd]] is a 6 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=4XXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XXD FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.41&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [https://pdbe.org/4xxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [https://www.ebi.ac.uk/pdbsum/4xxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xxd ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN] Defects in IGKC are the cause of immunoglobulin kappa light chain deficiency (IGKCD) [MIM:[https://omim.org/entry/614102 614102]. IGKCD is a disease characterized by the complete absence of immunoglobulin kappa chains.<ref>PMID:3931219</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Solanezumab (Eli Lilly) and crenezumab (Genentech) are the leading clinical antibodies targeting Amyloid-beta (Abeta) to be tested in multiple Phase III clinical trials for the prevention of Alzheimer's disease in at-risk individuals. Abeta capture by these clinical antibodies is explained here with the first reported mid-region Abeta-anti-Abeta complex crystal structure. Solanezumab accommodates a large Abeta epitope (960 A(2) buried interface over residues 16 to 26) that forms extensive contacts and hydrogen bonds to the antibody, largely via main-chain Abeta atoms and a deeply buried Phe19-Phe20 dipeptide core. The conformation of Abeta captured is an intermediate between observed sheet and helical forms with intramolecular hydrogen bonds stabilising residues 20-26 in a helical conformation. Remarkably, Abeta-binding residues are almost perfectly conserved in crenezumab. The structure explains the observed shared cross reactivity of solanezumab and crenezumab with proteins abundant in plasma that exhibit this Phe-Phe dipeptide.
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Authors: Hermans, S.J., Crespi, G.A.N., Parker, M.W., Miles, L.A.
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Molecular basis for mid-region amyloid-beta capture by leading Alzheimer's disease immunotherapies.,Crespi GA, Hermans SJ, Parker MW, Miles LA Sci Rep. 2015 Apr 16;5:9649. doi: 10.1038/srep09649. PMID:25880481<ref>PMID:25880481</ref>
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Description: Fab complex with Amyloid-beta
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Parker, M.W]]
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<div class="pdbe-citations 4xxd" style="background-color:#fffaf0;"></div>
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[[Category: Hermans, S.J]]
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== References ==
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[[Category: Crespi, G.A.N]]
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<references/>
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[[Category: Miles, L.A]]
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Crespi GAN]]
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[[Category: Hermans SJ]]
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[[Category: Miles LA]]
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[[Category: Parker MW]]

Current revision

Crystal Structure of mid-region amyloid beta capture by solanezumab

PDB ID 4xxd

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