1tch: Difference between revisions
No edit summary |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==STRUCTURE-ACTIVITY RELATIONSHIPS OF MU-CONOTOXIN GIIIA: STRUCTURE DETERMINATION OF ACTIVE AND INACTIVE SODIUM CHANNEL BLOCKER PEPTIDES BY NMR AND SIMULATED ANNEALING CALCULATIONS== | ==STRUCTURE-ACTIVITY RELATIONSHIPS OF MU-CONOTOXIN GIIIA: STRUCTURE DETERMINATION OF ACTIVE AND INACTIVE SODIUM CHANNEL BLOCKER PEPTIDES BY NMR AND SIMULATED ANNEALING CALCULATIONS== | ||
<StructureSection load='1tch' size='340' side='right' caption='[[1tch | <StructureSection load='1tch' size='340' side='right'caption='[[1tch]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1tch]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TCH OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[1tch]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TCH FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1tch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tch OCA], [https://pdbe.org/1tch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tch RCSB], [https://www.ebi.ac.uk/pdbsum/1tch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tch ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/CM3A_CONGE CM3A_CONGE] Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks Nav1.4/SCN4A. It also moderately blocks rNav1.1/SCN1A, rNav1.2/SCN2A, and mNav1.6/SCN8A. The inhibition is reversible. Induces paralysis in vertebrates.<ref>PMID:18950653</ref> <ref>PMID:21652775</ref> <ref>PMID:2410412</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 23: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Inagaki | [[Category: Large Structures]] | ||
[[Category: Kohda | [[Category: Inagaki F]] | ||
[[Category: Lancelin | [[Category: Kohda D]] | ||
[[Category: Lancelin J-M]] | |||
Latest revision as of 09:03, 5 July 2023
STRUCTURE-ACTIVITY RELATIONSHIPS OF MU-CONOTOXIN GIIIA: STRUCTURE DETERMINATION OF ACTIVE AND INACTIVE SODIUM CHANNEL BLOCKER PEPTIDES BY NMR AND SIMULATED ANNEALING CALCULATIONSSTRUCTURE-ACTIVITY RELATIONSHIPS OF MU-CONOTOXIN GIIIA: STRUCTURE DETERMINATION OF ACTIVE AND INACTIVE SODIUM CHANNEL BLOCKER PEPTIDES BY NMR AND SIMULATED ANNEALING CALCULATIONS
Structural highlights
FunctionCM3A_CONGE Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks Nav1.4/SCN4A. It also moderately blocks rNav1.1/SCN1A, rNav1.2/SCN2A, and mNav1.6/SCN8A. The inhibition is reversible. Induces paralysis in vertebrates.[1] [2] [3] Publication Abstract from PubMedA synthetic replacement study of the amino acid residues of mu-conotoxin GIIIA, a peptide blocker for muscle sodium channels, has recently shown that the conformation formed by three disulfide bridges and the molecular basicity, especially the one around the Arg13 residue, are important for blocking activity. In the present study, we determined the three-dimensional structure of an inactive analog, [Ala13]mu-conotoxin GIIIA, and refined that of the native toxin by NMR spectroscopy combined with simulated annealing calculations. The atomic root-mean-square difference of the mutant from the native conotoxin was 0.62 A for the backbone atoms (N, C alpha, C') of all residues except for the two terminal residues. The observation that the replacement of Arg13 by Ala13 does not significantly change the molecular conformation suggests that the loss of activity is not due to the conformational change but to the direct interaction of the essential Arg13 residue with the sodium channel molecules. In the determined structure, important residues for the activity, Arg13, Lys16, Hyp(hydroxyproline)17, and Arg19, are clustered on one side of the molecule, an observation which suggests that this face of the molecule associates with the receptor site of sodium channels. The hydroxyl group of Hyp17 is suggested to interact with the channel site with which the essential hydroxyl groups of tetrodotoxin and saxitoxin interact. Structure-activity relationships of mu-conotoxin GIIIA: structure determination of active and inactive sodium channel blocker peptides by NMR and simulated annealing calculations.,Wakamatsu K, Kohda D, Hatanaka H, Lancelin JM, Ishida Y, Oya M, Nakamura H, Inagaki F, Sato K Biochemistry. 1992 Dec 22;31(50):12577-84. PMID:1335283[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||