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| | ==Anti-methamphetamine single chain Fv in complex with MDMA== | | ==Anti-methamphetamine single chain Fv in complex with MDMA== |
| - | <StructureSection load='3gm0' size='340' side='right' caption='[[3gm0]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='3gm0' size='340' side='right'caption='[[3gm0]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3gm0]] is a 1 chain structure with sequence from [http://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=3GM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GM0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3gm0]] is a 1 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=3GM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GM0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=B41:(2S)-1-(1,3-BENZODIOXOL-5-YL)-N-METHYLPROPAN-2-AMINE'>B41</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3gkz|3gkz]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B41:(2S)-1-(1,3-BENZODIOXOL-5-YL)-N-METHYLPROPAN-2-AMINE'>B41</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IgG ([http://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'>[https://proteopedia.org/fgij/fg.htm?mol=3gm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gm0 OCA], [https://pdbe.org/3gm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gm0 RCSB], [https://www.ebi.ac.uk/pdbsum/3gm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gm0 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gm0 OCA], [http://pdbe.org/3gm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gm0 RCSB], [http://www.ebi.ac.uk/pdbsum/3gm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gm0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/3gm0_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gm/3gm0_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Celikel, R]] | + | [[Category: Mus musculus]] |
| - | [[Category: Owens, M]] | + | [[Category: Celikel R]] |
| - | [[Category: Peterson, E C]] | + | [[Category: Owens M]] |
| - | [[Category: Varughese, K I]] | + | [[Category: Peterson EC]] |
| - | [[Category: Anti-methamphetamine antibody]] | + | [[Category: Varughese KI]] |
| - | [[Category: Immune system]]
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| - | [[Category: Single chain fv]]
| + | |
| - | [[Category: Therapeutic antibody]]
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| 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 PubMed
Methamphetamine (METH) is a major drug threat in the United States and worldwide. Monoclonal antibody (mAb) therapy for treating METH abuse is showing exciting promise and the understanding of how mAb structure relates to function will be essential for future development of these important therapies. We have determined crystal structures of a high affinity anti-(+)-METH therapeutic single chain antibody fragment (scFv6H4, K(D)=10 nM) derived from one of our candidate mAb in complex with METH and the (+) stereoisomer of another abused drug, 3,4 methylenedioxy-N-methamphetamine (MDMA), known by the street name "ecstasy". The crystal structures revealed that scFv6H4 binds to METH and MDMA in a deep pocket that almost completely encases the drugs mostly through aromatic interactions. In addition, the cationic nitrogen of METH and MDMA forms a salt bridge with the carboxylate group of a glutamic acid residue and a hydrogen bond with a histidine side chain. Interestingly, there are two water molecules in the binding pocket and one of them is positioned for a C-H...O interaction with the aromatic ring of METH. These first crystal structures of a high affinity therapeutic antibody fragment against METH and MDMA (resolution = 1.9 A, and 2.4 A, respectively) provide a structural basis for designing the next generation of higher affinity antibodies and also for carrying out rational humanization.
Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse - methamphetamine and 3,4 methylenedioxy-N-methylamphetamine.,Celikel R, Peterson EC, Owens SM, Varughese KI Protein Sci. 2009 Sep 16. PMID:19760665[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Celikel R, Peterson EC, Owens SM, Varughese KI. Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse - methamphetamine and 3,4 methylenedioxy-N-methylamphetamine. Protein Sci. 2009 Sep 16. PMID:19760665 doi:10.1002/pro.244
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