3eys: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<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 [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3eys]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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='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> | <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> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A2NHM3_MOUSE A2NHM3_MOUSE] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 32: | Line 32: | ||
==See Also== | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | *[[3D structures of non-human antibody|3D structures of non-human antibody]] | ||
== References == | == References == | ||
| Line 38: | Line 39: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Dealwis | [[Category: Dealwis CG]] | ||
[[Category: Gardberg | [[Category: Gardberg AS]] | ||
Latest revision as of 03:26, 28 December 2023
PFA1 Fab fragment complexed with pyro-Glu3-A-Beta (3-8)PFA1 Fab fragment complexed with pyro-Glu3-A-Beta (3-8)
Structural highlights
FunctionEvolutionary 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
|
| ||||||||||||||||||