2uz6: Difference between revisions

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-[[Image:2uz6.jpg|left|200px]]
- {{Structure
+==AChBP-targeted a-conotoxin correlates distinct binding orientations with nAChR subtype selectivity.==
-|PDB= 2uz6 |SIZE=350|CAPTION= <scene name='initialview01'>2uz6</scene>, resolution 2.40&Aring;
+<StructureSection load='2uz6' size='340' side='right'caption='[[2uz6]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
-|SITE= <scene name='pdbsite=1:Gol+Binding+Site+For+Chain+G'>1</scene>
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>
+<table><tr><td colspan='2'>[[2uz6]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica] and [https://en.wikipedia.org/wiki/Conus_textile Conus textile]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2UZ6 FirstGlance]. <br>
-|ACTIVITY=
+</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>
-|GENE=
+<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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
-|DOMAIN=
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2uz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uz6 OCA], [https://pdbe.org/2uz6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2uz6 RCSB], [https://www.ebi.ac.uk/pdbsum/2uz6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2uz6 ProSAT]</span></td></tr>
-|RELATEDENTRY=[[2br7|2BR7]], [[2br8|2BR8]], [[2byn|2BYN]], [[2byp|2BYP]], [[2byq|2BYQ]], [[2byr|2BYR]], [[2bys|2BYS]], [[2c9t|2C9T]]
+</table>
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2uz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uz6 OCA], [http://www.ebi.ac.uk/pdbsum/2uz6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2uz6 RCSB]</span>
+== Function ==
-}}
+[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA]
+== 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/uz/2uz6_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=2uz6 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel alpha-conotoxin (alpha-TxIA) in the venom of Conus textile. Alpha-TxIA bound with high affinity to AChBPs from different species and selectively targeted the alpha(3)beta(2) nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20 degrees backbone tilt compared to other AChBP-conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases.
-'''ACHBP-TARGETED A-CONOTOXIN CORRELATES DISTINCT BINDING ORIENTATIONS WITH NACHR SUBTYPE SELECTIVITY.'''
+AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity.,Dutertre S, Ulens C, Buttner R, Fish A, van Elk R, Kendel Y, Hopping G, Alewood PF, Schroeder C, Nicke A, Smit AB, Sixma TK, Lewis RJ EMBO J. 2007 Aug 22;26(16):3858-67. Epub 2007 Jul 26. PMID:17660751<ref>PMID:17660751</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2uz6" style="background-color:#fffaf0;"></div>
-==Overview==
+==See Also==
-Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel alpha-conotoxin (alpha-TxIA) in the venom of Conus textile. Alpha-TxIA bound with high affinity to AChBPs from different species and selectively targeted the alpha(3)beta(2) nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20 degrees backbone tilt compared to other AChBP-conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases.
+*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-UZ6 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2UZ6 OCA].
+__TOC__
+</StructureSection>
-==Reference==
-AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity., Dutertre S, Ulens C, Buttner R, Fish A, van Elk R, Kendel Y, Hopping G, Alewood PF, Schroeder C, Nicke A, Smit AB, Sixma TK, Lewis RJ, EMBO J. 2007 Aug 22;26(16):3858-67. Epub 2007 Jul 26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17660751 17660751]
 [[Category: Aplysia californica]]
-[[Category: Protein complex]]
+[[Category: Conus textile]]
-[[Category: Alewood, P F.]]
+[[Category: Large Structures]]
-[[Category: Buttner, R.]]
+[[Category: Alewood PF]]
-[[Category: Dutertre, S.]]
+[[Category: Buttner R]]
-[[Category: Elk, R Van.]]
+[[Category: Dutertre S]]
-[[Category: Fish, A.]]
+[[Category: Fish A]]
-[[Category: Hopping, G.]]
+[[Category: Hopping G]]
-[[Category: Kendel, Y.]]
+[[Category: Kendel Y]]
-[[Category: Lewis, R J.]]
+[[Category: Lewis RJ]]
-[[Category: Nicke, A.]]
+[[Category: Nicke A]]
-[[Category: Schroeder, C.]]
+[[Category: Schroeder C]]
-[[Category: Sixma, T K.]]
+[[Category: Sixma TK]]
-[[Category: Smit, A B.]]
+[[Category: Smit AB]]
-[[Category: Ulens, C.]]
+[[Category: Ulens C]]
-[[Category: receptor]]
+[[Category: Van Elk R]]
-[[Category: soluble acetylcholine receptor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:06:30 2008''