1i7z

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(New page: 200px<br /> <applet load="1i7z" size="450" color="white" frame="true" align="right" spinBox="true" caption="1i7z, resolution 2.3&Aring;" /> '''ANTIBODY GNC92H2 BOU...)
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[[Image:1i7z.gif|left|200px]]<br />
 
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<applet load="1i7z" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1i7z, resolution 2.3&Aring;" />
 
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'''ANTIBODY GNC92H2 BOUND TO LIGAND'''<br />
 
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==Overview==
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==ANTIBODY GNC92H2 BOUND TO LIGAND==
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Murine monoclonal antibody GNC92H2 was elicited by active immunization, with a cocaine immunoconjugate and binds free cocaine with excellent, specificity and moderate affinity. Improvement of affinity, as well as, humanization of GNC92H2, would be advantageous in immunopharmacotherapy, for cocaine addiction, and for emergency cases of drug overdose. Toward, this end, the crystal structure of an engineered murine-human chimeric Fab, of GNC92H2 complexed with cocaine was determined at 2.3 A resolution., Structural analysis reveals a binding pocket with high shape and charge, complementarity to the cocaine framework, which explains the specificity, for cocaine, as opposed to the pharmacologically inactive cocaine, metabolites. Importantly, the structure provides a foundation for, mutagenesis to enhance the binding affinity for cocaine and potent cocaine, derivatives, such as cocaethylene, and for additional humanization of the, antibody.
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<StructureSection load='1i7z' size='340' side='right'caption='[[1i7z]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1i7z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I7Z FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COC:COCAINE'>COC</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1i7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i7z OCA], [https://pdbe.org/1i7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i7z RCSB], [https://www.ebi.ac.uk/pdbsum/1i7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i7z ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[https://www.uniprot.org/uniprot/IGKC_HUMAN IGKC_HUMAN]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i7/1i7z_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1i7z ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Murine monoclonal antibody GNC92H2 was elicited by active immunization with a cocaine immunoconjugate and binds free cocaine with excellent specificity and moderate affinity. Improvement of affinity, as well as humanization of GNC92H2, would be advantageous in immunopharmacotherapy for cocaine addiction, and for emergency cases of drug overdose. Toward this end, the crystal structure of an engineered murine-human chimeric Fab of GNC92H2 complexed with cocaine was determined at 2.3 A resolution. Structural analysis reveals a binding pocket with high shape and charge complementarity to the cocaine framework, which explains the specificity for cocaine, as opposed to the pharmacologically inactive cocaine metabolites. Importantly, the structure provides a foundation for mutagenesis to enhance the binding affinity for cocaine and potent cocaine derivatives, such as cocaethylene, and for additional humanization of the antibody.
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==Disease==
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Crystal structure of a cocaine-binding antibody.,Larsen NA, Zhou B, Heine A, Wirsching P, Janda KD, Wilson IA J Mol Biol. 2001 Aug 3;311(1):9-15. PMID:11469854<ref>PMID:11469854</ref>
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Known disease associated with this structure: Kappa light chain deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147200 147200]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1I7Z is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus_and_homo_sapiens Mus musculus and homo sapiens] with COC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1I7Z OCA].
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</div>
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<div class="pdbe-citations 1i7z" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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Crystal structure of a cocaine-binding antibody., Larsen NA, Zhou B, Heine A, Wirsching P, Janda KD, Wilson IA, J Mol Biol. 2001 Aug 3;311(1):9-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11469854 11469854]
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<references/>
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[[Category: Mus musculus and homo sapiens]]
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__TOC__
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[[Category: Protein complex]]
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</StructureSection>
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[[Category: Larsen, N.A.]]
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[[Category: Homo sapiens]]
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[[Category: Wilson, I.A.]]
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[[Category: Large Structures]]
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[[Category: COC]]
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[[Category: Mus musculus]]
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[[Category: antibody]]
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[[Category: Larsen NA]]
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[[Category: chimera]]
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[[Category: Wilson IA]]
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[[Category: igg fold]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:27:22 2007''
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Current revision

ANTIBODY GNC92H2 BOUND TO LIGAND

PDB ID 1i7z

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