We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

1e74

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 06:25, 2 March 2023

NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1 POINT MUTATION VARIANT R11E

Structural highlights

1e74 is a 1 chain structure with sequence from Conus imperialis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CA1_CONIM Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.^[1]

Publication Abstract from PubMed

alpha-Conotoxins are small disulfide-constrained peptide toxins which act as antagonists at specific subtypes of nicotinic acetylcholine receptors (nACh receptors). In this study, we analyzed the structures and activities of three mutants of alpha-conotoxin ImI, a 12 amino acid peptide active at alpha7 nACh receptors, in order to gain insight into the primary and tertiary structural requirements of neuronal alpha-conotoxin specificity. NMR solution structures were determined for mutants R11E, R7L, and D5N, resulting in representative ensembles of 20 conformers with average pairwise RMSD values of 0.46, 0.52, and 0.62 A from their mean structures, respectively, for the backbone atoms N, C(alpha), and C' of residues 2-11. The R11E mutant was found to have activity near that of wild-type ImI, while R7L and D5N demonstrated activities reduced by at least two orders of magnitude. Comparison of the structures reveals a common two-loop architecture, with variations observed in backbone and side-chain dihedral angles as well as surface electrostatic potentials upon mutation. Correlation of these structures and activities with those from previously published studies emphasizes that existing hypotheses regarding the molecular determinants of alpha-conotoxin specificity are not adequate for explaining peptide activity, and suggests that more subtle features, visualized here at the atomic level, are important for receptor binding. These data, in conjunction with reported characterizations of the acetylcholine binding site, support a model of toxin activity in which a single solvent-accessible toxin side-chain anchors the complex, with supporting weak interactions determining both the efficacy and the subtype specificity of the inhibitory activity.

Structure-activity relationships in a peptidic alpha7 nicotinic acetylcholine receptor antagonist.,Rogers JP, Luginbuhl P, Pemberton K, Harty P, Wemmer DE, Stevens RC J Mol Biol. 2000 Dec 15;304(5):911-26. PMID:11124036^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McIntosh JM, Yoshikami D, Mahe E, Nielsen DB, Rivier JE, Gray WR, Olivera BM. A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI. J Biol Chem. 1994 Jun 17;269(24):16733-9. PMID:8206995
↑ Rogers JP, Luginbuhl P, Pemberton K, Harty P, Wemmer DE, Stevens RC. Structure-activity relationships in a peptidic alpha7 nicotinic acetylcholine receptor antagonist. J Mol Biol. 2000 Dec 15;304(5):911-26. PMID:11124036 doi:10.1006/jmbi.2000.4247

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1e74"

@@ Line 1: / Line 1: @@
 ==NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1 POINT MUTATION VARIANT R11E==
-<StructureSection load='1e74' size='340' side='right'caption='[[1e74]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='1e74' size='340' side='right'caption='[[1e74]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1e74]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E74 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1e74]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_imperialis Conus imperialis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E74 FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+</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></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1e75|1e75]], [[1e76|1e76]], [[1im1|1im1]], [[1imi|1imi]], [[1cnl|1cnl]]</div></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=1e74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e74 OCA], [https://pdbe.org/1e74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e74 RCSB], [https://www.ebi.ac.uk/pdbsum/1e74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e74 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/CA1_CONIM CA1_CONIM]] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.<ref>PMID:8206995</ref>
+[https://www.uniprot.org/uniprot/CA1_CONIM CA1_CONIM] Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits. Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.<ref>PMID:8206995</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Conus imperialis]]
 [[Category: Large Structures]]
-[[Category: Harty, P]]
+[[Category: Harty P]]
-[[Category: Luginbuhl, P]]
+[[Category: Luginbuhl P]]
-[[Category: Pemberton, K]]
+[[Category: Pemberton K]]
-[[Category: Rogers, J P]]
+[[Category: Rogers JP]]
-[[Category: Stevens, R C]]
+[[Category: Stevens RC]]
-[[Category: Wemmer, D E]]
+[[Category: Wemmer DE]]
-[[Category: Alpha-conotoxin]]
-[[Category: Neuronal nicotinic acetylcholine receptor antagonist]]
-[[Category: Neurotoxin]]
-[[Category: Nmr solution structure]]
-[[Category: Peptide toxin]]

1e74

From Proteopedia

Revision as of 06:25, 2 March 2023

NMR SOLUTION STRUCTURE OF ALPHA-CONOTOXIN IM1 POINT MUTATION VARIANT R11E

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox