2br8: Difference between revisions

No edit summary
No edit summary
 
(21 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2br8.gif|left|200px]]<br />
<applet load="2br8" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2br8, resolution 2.40&Aring;" />
'''CRYSTAL STRUCTURE OF ACETYLCHOLINE-BINDING PROTEIN (ACHBP) FROM APLYSIA CALIFORNICA IN COMPLEX WITH AN ALPHA-CONOTOXIN PNIA VARIANT'''<br />


==Overview==
==Crystal Structure of Acetylcholine-binding Protein (AChBP) from Aplysia californica in complex with an alpha-conotoxin PnIA variant==
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 ... [[http://ispc.weizmann.ac.il/pmbin/getpm?15951818 (full description)]]
<StructureSection load='2br8' size='340' side='right'caption='[[2br8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<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>
</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=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=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>
</table>
== 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/br/2br8_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=2br8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==About this Structure==
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>
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]]. Structure known Active Site: AC1. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BR8 OCA]].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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]
</div>
<div class="pdbe-citations 2br8" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aplysia californica]]
[[Category: Aplysia californica]]
[[Category: Protein complex]]
[[Category: Conus pennaceus]]
[[Category: Bertrand, D.]]
[[Category: Large Structures]]
[[Category: Celie, P.H.N.]]
[[Category: Bertrand D]]
[[Category: Elk, R.Van.]]
[[Category: Celie PHN]]
[[Category: Hogg, R.C.]]
[[Category: Hogg RC]]
[[Category: Kasheverov, I.E.]]
[[Category: Kasheverov IE]]
[[Category: Mordvintsev, D.Y.]]
[[Category: Mordvintsev DY]]
[[Category: Nierop, P.Van.]]
[[Category: Sixma TK]]
[[Category: Rossum-Fikkert, S.E.Van.]]
[[Category: Smit AB]]
[[Category: Sixma, T.K.]]
[[Category: Tsetlin V]]
[[Category: Smit, A.B.]]
[[Category: Zhmak MN]]
[[Category: Tsetlin, V.]]
[[Category: Van Elk R]]
[[Category: Zhmak, M.N.]]
[[Category: Van Nierop P]]
[[Category: NH2]]
[[Category: Van Rossum-Fikkert SE]]
[[Category: SO4]]
[[Category: acetylcholine receptor inhibitor]]
[[Category: alpha-conotoxin]]
[[Category: amidation]]
[[Category: glycoprotein]]
[[Category: igg-fold]]
[[Category: immunoglobulin domain]]
[[Category: neurotoxin]]
[[Category: nicotinic receptor]]
[[Category: pentamer]]
[[Category: postsynaptic neurotoxin]]
[[Category: receptor]]
[[Category: receptor/inhibitor complex]]
[[Category: sulfation]]
[[Category: toxin]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Oct 30 16:45:43 2007''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA