2br8

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[[Image:2br8.gif|left|200px]]<br /><applet load="2br8" size="450" 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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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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<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 ==
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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 SO4 and NH2 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://ispc.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://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:56:05 2007''
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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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