View source for 3era


==RECOMBINANT ERABUTOXIN A (S8T MUTANT)==
<StructureSection load='3era' size='340' side='right'caption='[[3era]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3era]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Laticauda_semifasciata Laticauda semifasciata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ERA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ERA 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=3era FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3era OCA], [https://pdbe.org/3era PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3era RCSB], [https://www.ebi.ac.uk/pdbsum/3era PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3era ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/3S1EA_LATSE 3S1EA_LATSE] Binds with high affinity to muscular nicotinic acetylcholine receptors (nAChRs) (tested on Torpedo marmorata, Kd=21 uM) and with low affinity to neuronal alpha-7/CHRNA7 nAChRs (tested on chimeric alpha-7/CHRNA7, Kd=0.07 nM) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular transmission (PubMed:7721859). Blocks the extracellular increase of dopamine evoked by nicotine at 4.2 uM concentrations (PubMed:9840221). In vivo, produces peripheral paralysis.<ref>PMID:7721859</ref> <ref>PMID:9305882</ref> <ref>PMID:9840221</ref> 
== 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/er/3era_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=3era ConSurf].
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== Publication Abstract from PubMed ==
A previous mutational analysis of erabutoxin a (Ea), a curaremimetic toxin from sea snake venom, showed that the substitutions S8G and S8T caused, respectively, 176-fold and 780-fold affinity decreases for the nicotinic acetylcholine receptor (AchR). In view of the fact that the side-chain of Ser8 is buried in the wild-type toxin, we wondered whether these affinity changes reflect a direct binding contribution of S8 to the receptor and/or conformational changes that could have occurred in Ea as a result of the introduced mutations. To approach this question, we solved X-ray structures of the two mutants S8G and S8T at high resolution (0.18 nm and 0.17 nm, with R factors of 18.0% and 17.9%, respectively). The data show that none of the mutations significantly modified the toxin structure. Even within the site where the toxin binds to the receptor the backbone conformation remained unchanged. Therefore, the low affinities of the mutants S8T and S8G cannot be explained by a large conformational change of the toxin structure. Although we cannot exclude the possibility that undetectable structural changes have occurred in the toxin mutants, our data support the view that, although buried between loop I and II, S8 is part of the functional epitope of the toxin.

High resolution x-ray analysis of two mutants of a curaremimetic snake toxin.,Gaucher JF, Menez R, Arnoux B, Pusset J, Ducruix A Eur J Biochem. 2000 Mar;267(5):1323-9. PMID:10691969<ref>PMID:10691969</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3era" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Laticauda semifasciata]]
[[Category: Arnoux B]]
[[Category: Ducruix A]]
[[Category: Gaucher JF]]
[[Category: Menez A]]
[[Category: Menez R]]