7n43: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==== | ==Alpha-conotoxin OmIA with unusual pharmacological properties at alpha7 nicotinic receptors== | ||
<StructureSection load='7n43' size='340' side='right'caption='[[7n43]]' scene=''> | <StructureSection load='7n43' size='340' side='right'caption='[[7n43]], [[Resolution|resolution]] 2.47Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7n43]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_omaria Conus omaria] and [https://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N43 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N43 FirstGlance]. <br> | ||
</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=7n43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n43 OCA], [https://pdbe.org/7n43 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n43 RCSB], [https://www.ebi.ac.uk/pdbsum/7n43 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n43 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.47Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7n43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n43 OCA], [https://pdbe.org/7n43 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n43 RCSB], [https://www.ebi.ac.uk/pdbsum/7n43 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n43 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/ACHP_LYMST ACHP_LYMST] Binds to acetylcholine. Modulates neuronal synaptic transmission. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
OmIA, isolated from Conus omaria venom, is a potent antagonist at alpha7 nAChRs. We determined the co-crystal structure of OmIA with Lymnae stagnalis acetylcholine binding protein (Ls-AChBP) that identified His5, Val10 and Asn11 as key determinants for the high potency of OmIA at alpha7 nAChRs. Remarkably, despite a competitive binding mode observed in the co-crystal structure, OmIA and analogues displayed functional insurmountable antagonism at alpha7 and alpha3beta4 nAChRs, except OmIA analogues having long side chain at position 10 ([V10Q]OmIA and [V10L]OmIA), which were partial insurmountable antagonist at alpha7 nAChRs in the presence of type II positive allosteric modulators (PAMs). A "two-state, two-step" model was used to explain these observations, with [V10Q]OmIA and [V10L]OmIA co-existing in a fast reversible/surmountable as well as a tight binding/insurmountable state. OmIA and analogues also showed biphasic-inhibition at alpha7 nAChRs in the presence of PNU120596, with a preference for the high-affinity binding site following prolonged exposure. The molecular basis of binding and complex pharmacological profile of OmIA at alpha7 nAChRs presented in here expands on the potential of alpha-conotoxins to probe the pharmacological properties of nAChRs and may help guide the development novel alpha7 modulators. | |||
Unique Pharmacological Properties of alpha-Conotoxin OmIA at alpha7 nAChRs.,Ho TNT, Abraham N, Lewis RJ Front Pharmacol. 2021 Dec 8;12:803397. doi: 10.3389/fphar.2021.803397. , eCollection 2021. PMID:34955864<ref>PMID:34955864</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7n43" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Conus omaria]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Lymnaea stagnalis]] | ||
[[Category: Abraham N]] | |||
[[Category: Ho TNT]] | |||
[[Category: Lewis RJ]] | |||
Latest revision as of 16:24, 18 October 2023
Alpha-conotoxin OmIA with unusual pharmacological properties at alpha7 nicotinic receptors
| ||||||||||||
