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4xxd
From Proteopedia
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| - | ''' | + | ==Crystal Structure of mid-region amyloid beta capture by solanezumab== |
| + | <StructureSection load='4xxd' size='340' side='right' caption='[[4xxd]], [[Resolution|resolution]] 2.41Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4xxd]] is a 6 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XXD 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=4xxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xxd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4xxd RCSB], [http://www.ebi.ac.uk/pdbsum/4xxd PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | [[Category: | + | <references/> |
| - | [[Category: Parker, M | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Crespi, G A.N]] |
| - | [[Category: | + | [[Category: Hermans, S J]] |
| + | [[Category: Miles, L A]] | ||
| + | [[Category: Parker, M W]] | ||
| + | [[Category: Amyloid-beta]] | ||
| + | [[Category: Fab]] | ||
| + | [[Category: Immune system]] | ||
Revision as of 11:37, 30 April 2015
Crystal Structure of mid-region amyloid beta capture by solanezumab
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