FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2009889590> ?p ?o ?g. }

• W2009889590 endingPage "43924" @default.
• W2009889590 startingPage "43913" @default.
• W2009889590 abstract "Ivermectin is an anthelmintic drug that works by activating glutamate-gated chloride channel receptors (GluClRs) in nematode parasites. GluClRs belong to the Cys-loop receptor family that also includes glycine receptor (GlyR) chloride channels. GluClRs and A288G mutant GlyRs are both activated by low nanomolar ivermectin concentrations. The crystal structure of the Caenorhabditis elegans α GluClR complexed with ivermectin has recently been published. Here, we probed ivermectin sensitivity determinants on the α1 GlyR using site-directed mutagenesis and electrophysiology. Based on a mutagenesis screen of transmembrane residues, we identified Ala288 and Pro230 as crucial sensitivity determinants. A comparison of the actions of selamectin and ivermectin suggested the benzofuran C05-OH was required for high efficacy. When taken together with docking simulations, these results supported a GlyR ivermectin binding orientation similar to that seen in the GluClR crystal structure. However, whereas the crystal structure shows that ivermectin interacts with the α GluClR via H-bonds with Leu218, Ser260, and Thr285 (α GluClR numbering), our data indicate that H-bonds with residues homologous to Ser260 and Thr285 are not important for high ivermectin sensitivity or direct agonist efficacy in A288G α1 GlyRs or three other GluClRs. Our data also suggest that van der Waals interactions between the ivermectin disaccharide and GlyR M2-M3 loop residues are unimportant for high ivermectin sensitivity. Thus, although our results corroborate the ivermectin binding orientation as revealed by the crystal structure, they demonstrate that some of the binding interactions revealed by this structure do not pertain to other highly ivermectin-sensitive Cys-loop receptors." @default.
• W2009889590 created "2016-06-24" @default.
• W2009889590 creator A5024619779 @default.
• W2009889590 creator A5027657793 @default.
• W2009889590 creator A5065242834 @default.
• W2009889590 creator A5070653919 @default.
• W2009889590 creator A5078695405 @default.
• W2009889590 date "2011-12-01" @default.
• W2009889590 modified "2023-10-07" @default.
• W2009889590 title "Molecular Determinants of Ivermectin Sensitivity at the Glycine Receptor Chloride Channel" @default.
• W2009889590 cites W1487689711 @default.
• W2009889590 cites W1504812383 @default.
• W2009889590 cites W1552918907 @default.
• W2009889590 cites W1561436076 @default.
• W2009889590 cites W1788430178 @default.
• W2009889590 cites W1959467500 @default.
• W2009889590 cites W1963766570 @default.
• W2009889590 cites W1967233387 @default.
• W2009889590 cites W1970096466 @default.
• W2009889590 cites W1971191923 @default.
• W2009889590 cites W1971524852 @default.
• W2009889590 cites W1971857963 @default.
• W2009889590 cites W1973722820 @default.
• W2009889590 cites W1975239375 @default.
• W2009889590 cites W1990559461 @default.
• W2009889590 cites W1991859288 @default.
• W2009889590 cites W1999793963 @default.
• W2009889590 cites W2001095912 @default.
• W2009889590 cites W2017227716 @default.
• W2009889590 cites W2038365622 @default.
• W2009889590 cites W2042884038 @default.
• W2009889590 cites W2056174828 @default.
• W2009889590 cites W2057264061 @default.
• W2009889590 cites W2059230624 @default.
• W2009889590 cites W2062109199 @default.
• W2009889590 cites W2063149746 @default.
• W2009889590 cites W2063157730 @default.
• W2009889590 cites W2064551035 @default.
• W2009889590 cites W2068482739 @default.
• W2009889590 cites W2072378908 @default.
• W2009889590 cites W2076120537 @default.
• W2009889590 cites W2078023329 @default.
• W2009889590 cites W2084167390 @default.
• W2009889590 cites W2090058279 @default.
• W2009889590 cites W2090402915 @default.
• W2009889590 cites W2092160171 @default.
• W2009889590 cites W2098899569 @default.
• W2009889590 cites W2119974492 @default.
• W2009889590 cites W2124102028 @default.
• W2009889590 cites W2131378880 @default.
• W2009889590 cites W2136037216 @default.
• W2009889590 cites W2143014450 @default.
• W2009889590 cites W2146263980 @default.
• W2009889590 cites W2176819629 @default.
• W2009889590 doi "https://doi.org/10.1074/jbc.m111.262634" @default.
• W2009889590 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3243547" @default.
• W2009889590 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22033924" @default.
• W2009889590 hasPublicationYear "2011" @default.
• W2009889590 type Work @default.
• W2009889590 sameAs 2009889590 @default.
• W2009889590 citedByCount "54" @default.
• W2009889590 countsByYear W20098895902012 @default.
• W2009889590 countsByYear W20098895902013 @default.
• W2009889590 countsByYear W20098895902014 @default.
• W2009889590 countsByYear W20098895902015 @default.
• W2009889590 countsByYear W20098895902016 @default.
• W2009889590 countsByYear W20098895902017 @default.
• W2009889590 countsByYear W20098895902018 @default.
• W2009889590 countsByYear W20098895902019 @default.
• W2009889590 countsByYear W20098895902020 @default.
• W2009889590 countsByYear W20098895902021 @default.
• W2009889590 countsByYear W20098895902022 @default.
• W2009889590 countsByYear W20098895902023 @default.
• W2009889590 crossrefType "journal-article" @default.
• W2009889590 hasAuthorship W2009889590A5024619779 @default.
• W2009889590 hasAuthorship W2009889590A5027657793 @default.
• W2009889590 hasAuthorship W2009889590A5065242834 @default.
• W2009889590 hasAuthorship W2009889590A5070653919 @default.
• W2009889590 hasAuthorship W2009889590A5078695405 @default.
• W2009889590 hasBestOaLocation W20098895901 @default.
• W2009889590 hasConcept C105702510 @default.
• W2009889590 hasConcept C107824862 @default.
• W2009889590 hasConcept C118892022 @default.
• W2009889590 hasConcept C12554922 @default.
• W2009889590 hasConcept C145822097 @default.
• W2009889590 hasConcept C159110408 @default.
• W2009889590 hasConcept C170493617 @default.
• W2009889590 hasConcept C185592680 @default.
• W2009889590 hasConcept C2777499811 @default.
• W2009889590 hasConcept C2777756961 @default.
• W2009889590 hasConcept C2780535491 @default.
• W2009889590 hasConcept C35599011 @default.
• W2009889590 hasConcept C41685203 @default.
• W2009889590 hasConcept C515207424 @default.
• W2009889590 hasConcept C55493867 @default.
• W2009889590 hasConcept C71240020 @default.
• W2009889590 hasConcept C71924100 @default.
• W2009889590 hasConcept C86803240 @default.

• next