3eys: Difference between revisions
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<StructureSection load='3eys' size='340' side='right'caption='[[3eys]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='3eys' size='340' side='right'caption='[[3eys]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3eys]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3eys]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EYS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EYS FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eyu|3eyu]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3eyu|3eyu]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Igk-C ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Igk-C ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3eys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3eys OCA], [https://pdbe.org/3eys PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3eys RCSB], [https://www.ebi.ac.uk/pdbsum/3eys PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3eys ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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==See Also== | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 12:19, 23 February 2022
PFA1 Fab fragment complexed with pyro-Glu3-A-Beta (3-8)PFA1 Fab fragment complexed with pyro-Glu3-A-Beta (3-8)
Structural highlights
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 PubMedPassive immunotherapy (PI) is being explored as a potential therapeutic against Alzheimer's disease. The most promising antibodies (Abs) used in PI target the EFRH motif of the Abeta N-terminus. The monoclonal anti-Abeta Ab PFA1 recognizes the EFRH epitope of Abeta. PFA1 has a high affinity for Abeta fibrils and protofibrils (0.1 nM), as well as good affinity for Abeta monomers (20 nM). However, PFA1 binds the toxic N-terminally modified pyro-glutamate peptide pyro-Glu3-Abeta with a 77-fold loss in affinity compared to the WT Abeta(1-8). Furthermore, our earlier work illustrated PFA-1's potential for cross-reactivity. The receptor tyrosine kinaseRor2 which plays a role in skeletal and bone formation possesses the EFRH sequence. In fact, the PFA1 Fab binds the Ror2 peptide REEFRHEA with a 3-fold enhancement over WT Abeta(1-8). In this paper, the crystal structures of the hybridoma-derived PFA1 Fab in complex with pyro-Glu3-Abetapeptide and with a cross-reacting peptide from Ror2 have been determined at resolutions of 1.95 and 2.7 A, respectively. As with wild type Abeta, these peptides bind to the Fab via a combination of charge- and shape-complementarity, hydrogen bonding, and hydrophobic interactions. Comparison of the structures of the four peptides Abeta(1-8), Grip1, pyro-Glu3-Abeta and Ror2 in complex with PFA-1 show that the greatest conformational flexibility occur at residues 2-3 and 8 of the peptide. These structures provide a molecular basis of the specificity tolerance of PFA1, and its ability to recognize Abeta N-terminal heterogeneity. The structures provide clues to improving mAb specificity and affinity for pyro-Glutamate Abeta. THE X-RAY STRUCTURES OF AMYLOID BETA-RELATED PEPTIDES COMPLEXED TO ANTIBODIES.,Gardberg AS, Dice L, Pridgen K, Ko J, Patterson P, Ou S, Wetzel R, Dealwis C Biochemistry. 2009 Apr 22. PMID:19385664[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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