7dji: Difference between revisions

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<StructureSection load='7dji' size='340' side='right'caption='[[7dji]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='7dji' size='340' side='right'caption='[[7dji]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7dji]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DJI FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DJI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DJI FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H8U:Paraherquamide+A'>H8U</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H8U:Paraherquamide+A'>H8U</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7dji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dji OCA], [https://pdbe.org/7dji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dji RCSB], [https://www.ebi.ac.uk/pdbsum/7dji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dji ProSAT]</span></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=7dji FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dji OCA], [https://pdbe.org/7dji PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dji RCSB], [https://www.ebi.ac.uk/pdbsum/7dji PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dji 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 ==
The anthelmintic paraherquamide A acts selectively on the nematode L-type nicotinic acetylcholine receptors (nAChRs) but the mechanism of its selectivity is unknown. This study targeted the basis of paraherquamide A selectivity by determining an X-ray crystal structure of the acetylcholine binding protein (AChBP), a surrogate nAChR ligand-binding domain, complexed with the compound and by measuring its actions on wild-type and mutant Caenorhabditis elegans nematodes and functionally expressed C. elegans nAChRs. Paraherquamide A showed a higher efficacy for the levamisole-sensitive (L-type (UNC-38/UNC-29/UNC-63/LEV8/LEV-1)) nAChR than the nicotine-sensitive (N-type (ACR-16)) nAChR, a result consistent with in vivo studies on wild type worms and worms with mutations in subunits of these two classes of receptors. The X-ray crystal structure of the Ls-AChBP-paraherquamide A complex and site-directed amino acid mutation studies showed for the first time that loop C, loop E and loop F of the orthosteric receptor binding site play critical roles in the observed L-type nAChR selective actions of paraherquamide A. Significance Statement Paraherquamide A, an oxindole alkaloid, has been shown to act selectively on the L-type over N-type nAChRs in nematodes, but the mechanism of selectivity is unknown. We have co-crystallized paraherquamide A with the acetylcholine binding protein, a surrogate of nAChRs, and found that structural features of loop C, loop E and loop F contribute to the L-type nAChR selectivity of the alkaloid. The results create a new platform for the design of anthelmintic drugs targeting cholinergic neurotransmission in parasitic nematodes.
Determinants of subtype-selectivity of the anthelmintic paraherquamide A on Caenorhabditis elegans nicotinic acetylcholine receptors.,Koizumi W, Otsubo S, Furutani S, Niki K, Takayama K, Fujimura S, Maekawa T, Koyari R, Ihara M, Kai K, Hayashi H, Ali MS, Kage-Nakadai E, Sattelle DB, Matsuda K Mol Pharmacol. 2023 Mar 22:MOLPHARM-AR-2022-000601. doi: , 10.1124/molpharm.122.000601. PMID:36948535<ref>PMID:36948535</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dji" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lymnaea stagnalis]]
[[Category: Ihara M]]
[[Category: Ihara M]]
[[Category: Matsuda K]]
[[Category: Matsuda K]]

Latest revision as of 10:57, 23 October 2024

Crystal structure of Lymnaea stagnalis Acetylcholine binding protein (AChBP) complexed with Paraherquamide A

7dji, resolution 2.20Å

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