3eys: Difference between revisions

No edit summary
No edit summary
 
(8 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{Seed}}
[[Image:3eys.jpg|left|200px]]


<!--
==PFA1 Fab fragment complexed with pyro-Glu3-A-Beta (3-8)==
The line below this paragraph, containing "STRUCTURE_3eys", creates the "Structure Box" on the page.
<StructureSection load='3eys' size='340' side='right'caption='[[3eys]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)  
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</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>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene></td></tr>
{{STRUCTURE_3eys|  PDB=3eys  |  SCENE=  }}
<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>
== Function ==
[https://www.uniprot.org/uniprot/A2NHM3_MOUSE A2NHM3_MOUSE]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ey/3eys_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3eys ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Passive 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.


===PFA1 Fab fragment complexed with pyro-Glu3-A-Beta (3-8)===
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<ref>PMID:19385664</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3eys" style="background-color:#fffaf0;"></div>


<!--
==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_19385664}}, adds the Publication Abstract to the page
*[[Antibody 3D structures|Antibody 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 19385664 is the PubMed ID number.
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
-->
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
{{ABSTRACT_PUBMED_19385664}}
== References ==
 
<references/>
==About this Structure==
__TOC__
3EYS is a 3 chains structure of sequences from [http://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].
</StructureSection>
 
[[Category: Large Structures]]
==Reference==
<ref group="xtra">PMID:19385664</ref><references group="xtra"/>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Dealwis, C G.]]
[[Category: Dealwis CG]]
[[Category: Gardberg, A S.]]
[[Category: Gardberg AS]]
[[Category: Alzheimers']]
[[Category: Amyloid]]
[[Category: Fab]]
[[Category: Immune system]]
[[Category: Protein-peptide complex]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 13 10:14:16 2009''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA