1cly: Difference between revisions

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New page: left|200px<br /> <applet load="1cly" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cly, resolution 2.5Å" /> '''IGG FAB (HUMAN IGG1,...
 
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[[Image:1cly.gif|left|200px]]<br />
<applet load="1cly" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1cly, resolution 2.5&Aring;" />
'''IGG FAB (HUMAN IGG1, KAPPA) CHIMERIC FRAGMENT (CBR96) COMPLEXED WITH LEWIS Y NONOATE METHYL ESTER'''<br />


==Overview==
==IGG FAB (HUMAN IGG1, KAPPA) CHIMERIC FRAGMENT (CBR96) COMPLEXED WITH LEWIS Y NONOATE METHYL ESTER==
The crystal structures of the murine BR96 Fab and its human chimera have, been determined in complex with the nonoate methyl ester derivative of, Lewis Y (nLey) at 2.8 A and 2.5 A resolution, respectively. BR96 binds the, carbohydrate in a large pocket which is formed by residues of all CDR, loops except L2. The binding of the carbohydrate is mediated predominantly, by aromatic residues in BR96. Analysis of the structure suggests that BR96, is capable of recognizing a structure larger than the Le(y), tetrasaccharide, providing a possible explanation for its high tumour, selectivity. The structure provides a rationale for mutagenesis, experiments that have resulted in BR96 CDR loop mutants with increased, affinity for nLey and/or tumour cells.
<StructureSection load='1cly' size='340' side='right'caption='[[1cly]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1cly]] is a 2 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=1CLY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CLY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NON:METHYL+NONANOATE+(ESTER)'>NON</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=1cly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cly OCA], [https://pdbe.org/1cly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cly RCSB], [https://www.ebi.ac.uk/pdbsum/1cly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cly ProSAT]</span></td></tr>
</table>
== Disease ==
[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>
== Function ==
[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN]
== 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/cl/1cly_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1cly ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The crystal structures of the murine BR96 Fab and its human chimera have been determined in complex with the nonoate methyl ester derivative of Lewis Y (nLey) at 2.8 A and 2.5 A resolution, respectively. BR96 binds the carbohydrate in a large pocket which is formed by residues of all CDR loops except L2. The binding of the carbohydrate is mediated predominantly by aromatic residues in BR96. Analysis of the structure suggests that BR96 is capable of recognizing a structure larger than the Le(y) tetrasaccharide, providing a possible explanation for its high tumour selectivity. The structure provides a rationale for mutagenesis experiments that have resulted in BR96 CDR loop mutants with increased affinity for nLey and/or tumour cells.


==About this Structure==
The x-ray structure of an anti-tumour antibody in complex with antigen.,Jeffrey PD, Bajorath J, Chang CY, Yelton D, Hellstrom I, Hellstrom KE, Sheriff S Nat Struct Biol. 1995 Jun;2(6):466-71. PMID:7664109<ref>PMID:7664109</ref>
1CLY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NON as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CLY OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
The x-ray structure of an anti-tumour antibody in complex with antigen., Jeffrey PD, Bajorath J, Chang CY, Yelton D, Hellstrom I, Hellstrom KE, Sheriff S, Nat Struct Biol. 1995 Jun;2(6):466-71. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7664109 7664109]
</div>
<div class="pdbe-citations 1cly" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Bajorath, J.]]
[[Category: Bajorath J]]
[[Category: Sheriff, S.]]
[[Category: Sheriff S]]
[[Category: NON]]
[[Category: antib]]
[[Category: glycoprotein]]
[[Category: immunoglobulin]]
[[Category: immunoglobulin c region]]
 
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