2br8

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[[Image:2br8.gif|left|200px]]<br /><applet load="2br8" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2br8, resolution 2.40&Aring;" />
 
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'''CRYSTAL STRUCTURE OF ACETYLCHOLINE-BINDING PROTEIN (ACHBP) FROM APLYSIA CALIFORNICA IN COMPLEX WITH AN ALPHA-CONOTOXIN PNIA VARIANT'''<br />
 
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==Overview==
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==Crystal Structure of Acetylcholine-binding Protein (AChBP) from Aplysia californica in complex with an alpha-conotoxin PnIA variant==
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<StructureSection load='2br8' size='340' side='right'caption='[[2br8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2br8]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica] and [https://en.wikipedia.org/wiki/Conus_pennaceus Conus pennaceus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BR8 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]] 2.4&#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=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2br8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2br8 OCA], [https://pdbe.org/2br8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2br8 RCSB], [https://www.ebi.ac.uk/pdbsum/2br8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2br8 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA]
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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/br/2br8_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=2br8 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 ==
Conotoxins (Ctx) form a large family of peptide toxins from cone snail venoms that act on a broad spectrum of ion channels and receptors. The subgroup alpha-Ctx specifically and selectively binds to subtypes of nicotinic acetylcholine receptors (nAChRs), which are targets for treatment of several neurological disorders. Here we present the structure at a resolution of 2.4 A of alpha-Ctx PnIA (A10L D14K), a potent blocker of the alpha(7)-nAChR, bound with high affinity to acetylcholine binding protein (AChBP), the prototype for the ligand-binding domains of the nAChR superfamily. Alpha-Ctx is buried deep within the ligand-binding site and interacts with residues on both faces of adjacent subunits. The toxin itself does not change conformation, but displaces the C loop of AChBP and induces a rigid-body subunit movement. Knowledge of these contacts could facilitate the rational design of drug leads using the Ctx framework and may lead to compounds with increased receptor subtype selectivity.
Conotoxins (Ctx) form a large family of peptide toxins from cone snail venoms that act on a broad spectrum of ion channels and receptors. The subgroup alpha-Ctx specifically and selectively binds to subtypes of nicotinic acetylcholine receptors (nAChRs), which are targets for treatment of several neurological disorders. Here we present the structure at a resolution of 2.4 A of alpha-Ctx PnIA (A10L D14K), a potent blocker of the alpha(7)-nAChR, bound with high affinity to acetylcholine binding protein (AChBP), the prototype for the ligand-binding domains of the nAChR superfamily. Alpha-Ctx is buried deep within the ligand-binding site and interacts with residues on both faces of adjacent subunits. The toxin itself does not change conformation, but displaces the C loop of AChBP and induces a rigid-body subunit movement. Knowledge of these contacts could facilitate the rational design of drug leads using the Ctx framework and may lead to compounds with increased receptor subtype selectivity.
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==About this Structure==
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Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant.,Celie PH, Kasheverov IE, Mordvintsev DY, Hogg RC, van Nierop P, van Elk R, van Rossum-Fikkert SE, Zhmak MN, Bertrand D, Tsetlin V, Sixma TK, Smit AB Nat Struct Mol Biol. 2005 Jul;12(7):582-8. Epub 2005 Jun 12. PMID:15951818<ref>PMID:15951818</ref>
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2BR8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+E'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BR8 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant., Celie PH, Kasheverov IE, Mordvintsev DY, Hogg RC, van Nierop P, van Elk R, van Rossum-Fikkert SE, Zhmak MN, Bertrand D, Tsetlin V, Sixma TK, Smit AB, Nat Struct Mol Biol. 2005 Jul;12(7):582-8. Epub 2005 Jun 12. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15951818 15951818]
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</div>
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[[Category: Aplysia californica]]
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<div class="pdbe-citations 2br8" style="background-color:#fffaf0;"></div>
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[[Category: Protein complex]]
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[[Category: Bertrand, D.]]
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[[Category: Celie, P H.N.]]
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[[Category: Elk, R Van.]]
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[[Category: Hogg, R C.]]
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[[Category: Kasheverov, I E.]]
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[[Category: Mordvintsev, D Y.]]
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[[Category: Nierop, P Van.]]
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[[Category: Rossum-Fikkert, S E.Van.]]
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[[Category: Sixma, T K.]]
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[[Category: Smit, A B.]]
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[[Category: Tsetlin, V.]]
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[[Category: Zhmak, M N.]]
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[[Category: NH2]]
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[[Category: SO4]]
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[[Category: acetylcholine receptor inhibitor]]
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[[Category: alpha-conotoxin]]
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[[Category: amidation]]
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[[Category: glycoprotein]]
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[[Category: igg-fold]]
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[[Category: immunoglobulin domain]]
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[[Category: neurotoxin]]
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[[Category: nicotinic receptor]]
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[[Category: pentamer]]
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[[Category: postsynaptic neurotoxin]]
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[[Category: receptor]]
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[[Category: receptor/inhibitor complex]]
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[[Category: sulfation]]
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[[Category: toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:40:51 2008''
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==See Also==
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*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Aplysia californica]]
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[[Category: Conus pennaceus]]
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[[Category: Large Structures]]
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[[Category: Bertrand D]]
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[[Category: Celie PHN]]
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[[Category: Hogg RC]]
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[[Category: Kasheverov IE]]
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[[Category: Mordvintsev DY]]
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[[Category: Sixma TK]]
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[[Category: Smit AB]]
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[[Category: Tsetlin V]]
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[[Category: Zhmak MN]]
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[[Category: Van Elk R]]
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[[Category: Van Nierop P]]
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[[Category: Van Rossum-Fikkert SE]]

Current revision

Crystal Structure of Acetylcholine-binding Protein (AChBP) from Aplysia californica in complex with an alpha-conotoxin PnIA variant

PDB ID 2br8

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