2uz6: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2uz6]] is a 20 chain structure with sequence 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UZ6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[2uz6]] is a 20 chain structure with sequence 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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2UZ6 FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2br7|2br7]], [[2br8|2br8]], [[2byn|2byn]], [[2byp|2byp]], [[2byq|2byq]], [[2byr|2byr]], [[2bys|2bys]], [[2c9t|2c9t]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2br7|2br7]], [[2br8|2br8]], [[2byn|2byn]], [[2byp|2byp]], [[2byq|2byq]], [[2byr|2byr]], [[2bys|2bys]], [[2c9t|2c9t]]</td></tr> | ||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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.rcsb.org/pdb/explore.do?structureId=2uz6 RCSB], [http://www.ebi.ac.uk/pdbsum/2uz6 PDBsum]</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=2uz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uz6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2uz6 RCSB], [http://www.ebi.ac.uk/pdbsum/2uz6 PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Aplysia californica]] | [[Category: Aplysia californica]] | ||
[[Category: Alewood, P F | [[Category: Alewood, P F]] | ||
[[Category: Buttner, R | [[Category: Buttner, R]] | ||
[[Category: Dutertre, S | [[Category: Dutertre, S]] | ||
[[Category: Elk, R Van | [[Category: Elk, R Van]] | ||
[[Category: Fish, A | [[Category: Fish, A]] | ||
[[Category: Hopping, G | [[Category: Hopping, G]] | ||
[[Category: Kendel, Y | [[Category: Kendel, Y]] | ||
[[Category: Lewis, R J | [[Category: Lewis, R J]] | ||
[[Category: Nicke, A | [[Category: Nicke, A]] | ||
[[Category: Schroeder, C | [[Category: Schroeder, C]] | ||
[[Category: Sixma, T K | [[Category: Sixma, T K]] | ||
[[Category: Smit, A B | [[Category: Smit, A B]] | ||
[[Category: Ulens, C | [[Category: Ulens, C]] | ||
[[Category: Receptor-toxin complex]] | [[Category: Receptor-toxin complex]] | ||
Revision as of 17:40, 19 January 2015
AChBP-targeted a-conotoxin correlates distinct binding orientations with nAChR subtype selectivity.AChBP-targeted a-conotoxin correlates distinct binding orientations with nAChR subtype selectivity.
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 PubMedNeuronal 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 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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