7dji

<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>

</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>

== Function ==

[https://www.uniprot.org/uniprot/ACHP_LYMST ACHP_LYMST] Binds to acetylcholine. Modulates neuronal synaptic transmission.

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== 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>

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== References ==

<references/>

[[Category: Lymnaea stagnalis]]