This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

7n20

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

NMR structure of native AnIB

Structural highlights

7n20 is a 1 chain structure with sequence from Conus anemone. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CA1AB_CONAN Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic toxin blocks rat alpha-3beta-2/CHRNA3-CHRNB2 nAChRs (IC(50)=0.3 nM) and alpha-7/CHRNA7 nAChRs (IC(50)=76 nM).^[1] This synthetic toxin blocks rat alpha-3-beta-2/CHRNA3-CHRNB2 nAChRs (IC(50)=0.2 nM).^[2]

Publication Abstract from PubMed

Conotoxins are peptides found in the venoms of marine cone snails. They are typically highly structured and stable and have potent activities at nicotinic acetylcholine receptors, which make them valuable research tools and promising lead molecules for drug development. Many conotoxins are also highly modified with posttranslational modifications such as proline hydroxylation, glutamic acid gamma-carboxylation, tyrosine sulfation and C-terminal amidation, amongst others. The role of these posttranslational modifications is poorly understood, and it is unclear whether the modifications interact directly with the binding site, alter conotoxin structure, or both. Here we synthesised a set of twelve conotoxin variants bearing posttranslational modifications in the form of native sulfotyrosine and C-terminal amidation and show that these two modifications in combination increase their activity at nicotinic acetylcholine receptors and binding to soluble acetylcholine binding proteins, respectively. We then rationalise how these functional differences between variants might arise from stabilization of the three-dimensional structures and interactions with the binding sites, using high-resolution nuclear magnetic resonance data. This study demonstrates that posttranslational modifications can modulate interactions between a ligand and receptor by a combination of structural and binding alterations. A deeper mechanistic understanding of the role of posttranslational modifications in structure-activity relationships is essential for understanding receptor biology and could help to guide structure-based drug design.

Posttranslational modifications of alpha-conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding.,Ho TNT, Lee HS, Swaminathan S, Goodwin L, Rai N, Ushay B, Lewis RJ, Rosengren KJ, Conibear AC RSC Med Chem. 2021 Jul 26;12(9):1574-1584. doi: 10.1039/d1md00182e. eCollection, 2021 Sep 23. PMID:34671739^[3]

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

References

↑ Loughnan ML, Nicke A, Jones A, Adams DJ, Alewood PF, Lewis RJ. Chemical and functional identification and characterization of novel sulfated alpha-conotoxins from the cone snail Conus anemone. J Med Chem. 2004 Feb 26;47(5):1234-41. PMID:14971903 doi:10.1021/jm031010o
↑ Loughnan ML, Nicke A, Jones A, Adams DJ, Alewood PF, Lewis RJ. Chemical and functional identification and characterization of novel sulfated alpha-conotoxins from the cone snail Conus anemone. J Med Chem. 2004 Feb 26;47(5):1234-41. PMID:14971903 doi:10.1021/jm031010o
↑ Ho TNT, Lee HS, Swaminathan S, Goodwin L, Rai N, Ushay B, Lewis RJ, Rosengren KJ, Conibear AC. Posttranslational modifications of α-conotoxins: sulfotyrosine and C-terminal amidation stabilise structures and increase acetylcholine receptor binding. RSC Med Chem. 2021 Jul 26;12(9):1574-1584. PMID:34671739 doi:10.1039/d1md00182e

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/7n20"

Categories: Conus anemone | Large Structures | Conibear AC | Lee HS | Rosengren KJ

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7n20]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_anemone Conus anemone]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N20 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N20 FirstGlance]. <br>
-</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=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
+</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='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=TYS:O-SULFO-L-TYROSINE'>TYS</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=7n20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n20 OCA], [https://pdbe.org/7n20 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n20 RCSB], [https://www.ebi.ac.uk/pdbsum/7n20 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n20 ProSAT]</span></td></tr>
 </table>

7n20

From Proteopedia

Current revision

NMR structure of native AnIB

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox