2bag: Difference between revisions

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-[[Image:2bag.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_2bag", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
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-{{STRUCTURE_2bag|  PDB=2bag  |  SCENE=  }}
-'''3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine'''
+==3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine==
+<StructureSection load='2bag' size='340' side='right'caption='[[2bag]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2bag]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BAG 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]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=GSG:1S,3AS,8AS-TRIMETHYL-1-OXIDO-1,2,3,3A,8,8A-HEXAHYDROPYRROLO[2,3-B]INDOL-5-YL+2-ETHYLPHENYLCARBAMATE'>GSG</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=2bag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bag OCA], [https://pdbe.org/2bag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bag RCSB], [https://www.ebi.ac.uk/pdbsum/2bag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bag ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ACES_TETCF ACES_TETCF] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.
+== 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/ba/2bag_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=2bag ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ganstigmine is an orally active, geneserine derived, carbamate-based acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. The crystal structure of the ganstigmine conjugate with Torpedo californica acetylcholinesterase (TcAChE) has been determined at 2.40 A resolution, and a detailed structure-based analysis of the in vitro and ex vivo anti-AChE activity by ganstigmine and by new geneserine derivatives is presented. The carbamoyl moiety is covalently bound to the active-site serine, whereas the leaving group geneseroline is not retained in the catalytic pocket. The nitrogen atom of the carbamoyl moiety of ganstigmine is engaged in a key hydrogen-bonding interaction with the active site histidine (His440). This result offers an explanation for the inactivation of the catalytic triad and may account for the long duration of action of ganstigmine in vivo. The 3D structure also provides a structural framework for the design of compounds with improved binding affinity and pharmacological properties.
-==Overview==
+Structural determinants of Torpedo californica acetylcholinesterase inhibition by the novel and orally active carbamate based anti-alzheimer drug ganstigmine (CHF-2819).,Bartolucci C, Siotto M, Ghidini E, Amari G, Bolzoni PT, Racchi M, Villetti G, Delcanale M, Lamba D J Med Chem. 2006 Aug 24;49(17):5051-8. PMID:16913695<ref>PMID:16913695</ref>
-Ganstigmine is an orally active, geneserine derived, carbamate-based acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. The crystal structure of the ganstigmine conjugate with Torpedo californica acetylcholinesterase (TcAChE) has been determined at 2.40 A resolution, and a detailed structure-based analysis of the in vitro and ex vivo anti-AChE activity by ganstigmine and by new geneserine derivatives is presented. The carbamoyl moiety is covalently bound to the active-site serine, whereas the leaving group geneseroline is not retained in the catalytic pocket. The nitrogen atom of the carbamoyl moiety of ganstigmine is engaged in a key hydrogen-bonding interaction with the active site histidine (His440). This result offers an explanation for the inactivation of the catalytic triad and may account for the long duration of action of ganstigmine in vivo. The 3D structure also provides a structural framework for the design of compounds with improved binding affinity and pharmacological properties.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-BAG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BAG OCA].
+</div>
+<div class="pdbe-citations 2bag" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Structural determinants of Torpedo californica acetylcholinesterase inhibition by the novel and orally active carbamate based anti-alzheimer drug ganstigmine (CHF-2819)., Bartolucci C, Siotto M, Ghidini E, Amari G, Bolzoni PT, Racchi M, Villetti G, Delcanale M, Lamba D, J Med Chem. 2006 Aug 24;49(17):5051-8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16913695 16913695]
+*[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]]
-[[Category: Acetylcholinesterase]]
+== References ==
-[[Category: Single protein]]
+<references/>
-[[Category: Torpedo californica]]
+__TOC__
-[[Category: Bartolucci, C.]]
+</StructureSection>
-[[Category: Delcanale, M.]]
+[[Category: Large Structures]]
-[[Category: Lamba, D.]]
+[[Category: Tetronarce californica]]
-[[Category: Racchi, M.]]
+[[Category: Bartolucci C]]
-[[Category: Siotto, M.]]
+[[Category: Delcanale M]]
-[[Category: Villetti, G.]]
+[[Category: Lamba D]]
-[[Category: Anti-alzheimer drug]]
+[[Category: Racchi M]]
-[[Category: Cholinesterase]]
+[[Category: Siotto M]]
-[[Category: Neurotransmitter cleavage]]
+[[Category: Villetti G]]
-[[Category: Serine hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 20:02:27 2008''