FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313251268> ?p ?o ?g. }

• W4313251268 abstract "The drug praziquantel (PZQ) is the key clinical therapy for treating schistosomiasis and other infections caused by parasitic flatworms. A schistosome target for PZQ was recently identified- a transient receptor potential ion channel in the melastatin subfamily (TRPMPZQ)-however, little is known about the properties of TRPMPZQ in other parasitic flatworms. Here, TRPMPZQ orthologs were scrutinized from all currently available parasitic flatworm genomes. TRPMPZQ is present in all parasitic flatworms, and the consensus PZQ binding site was well conserved. Functional profiling of trematode, cestode, and a free-living flatworm TRPMPZQ ortholog revealed differing sensitives (~300-fold) of these TRPMPZQ channels toward PZQ, which matched the varied sensitivities of these different flatworms to PZQ. Three loci of variation were defined across the parasitic flatworm TRPMPZQ pocketome with the identity of an acidic residue in the TRP domain acting as a gatekeeper residue impacting PZQ residency within the TRPMPZQ ligand binding pocket. In trematodes and cyclophyllidean cestodes, which display high sensitivity to PZQ, this TRP domain residue is an aspartic acid which is permissive for potent activation by PZQ. However, the presence of a glutamic acid residue found in other parasitic and free-living flatworm TRPMPZQ was associated with lower sensitivity to PZQ. The definition of these different binding pocket architectures explains why PZQ shows high therapeutic effectiveness against specific fluke and tapeworm infections and will help the development of better tailored therapies toward other parasitic infections of humans, livestock, and fish." @default.
• W4313251268 created "2023-01-06" @default.
• W4313251268 creator A5018263796 @default.
• W4313251268 creator A5035289238 @default.
• W4313251268 creator A5037681035 @default.
• W4313251268 creator A5047013622 @default.
• W4313251268 creator A5074307523 @default.
• W4313251268 date "2022-12-27" @default.
• W4313251268 modified "2023-10-14" @default.
• W4313251268 title "Natural variation in the binding pocket of a parasitic flatworm TRPM channel resolves the basis for praziquantel sensitivity" @default.
• W4313251268 cites W102715436 @default.
• W4313251268 cites W144805995 @default.
• W4313251268 cites W154209531 @default.
• W4313251268 cites W1780297814 @default.
• W4313251268 cites W1891240969 @default.
• W4313251268 cites W1978947246 @default.
• W4313251268 cites W1981906828 @default.
• W4313251268 cites W1983094623 @default.
• W4313251268 cites W1983687734 @default.
• W4313251268 cites W1984759526 @default.
• W4313251268 cites W2014369576 @default.
• W4313251268 cites W2021671790 @default.
• W4313251268 cites W2025888597 @default.
• W4313251268 cites W2026256543 @default.
• W4313251268 cites W2031168104 @default.
• W4313251268 cites W2033286213 @default.
• W4313251268 cites W2035827103 @default.
• W4313251268 cites W2051368981 @default.
• W4313251268 cites W2059348203 @default.
• W4313251268 cites W2066990816 @default.
• W4313251268 cites W2069982778 @default.
• W4313251268 cites W2086324103 @default.
• W4313251268 cites W2091752317 @default.
• W4313251268 cites W2094255857 @default.
• W4313251268 cites W2100713606 @default.
• W4313251268 cites W2112126440 @default.
• W4313251268 cites W2120906891 @default.
• W4313251268 cites W2140852626 @default.
• W4313251268 cites W2143664654 @default.
• W4313251268 cites W2149655632 @default.
• W4313251268 cites W2223370383 @default.
• W4313251268 cites W2411054862 @default.
• W4313251268 cites W2412143483 @default.
• W4313251268 cites W2436281318 @default.
• W4313251268 cites W2529485338 @default.
• W4313251268 cites W2559577985 @default.
• W4313251268 cites W2565541933 @default.
• W4313251268 cites W2567204400 @default.
• W4313251268 cites W2766911789 @default.
• W4313251268 cites W2802489789 @default.
• W4313251268 cites W2823472156 @default.
• W4313251268 cites W2890806040 @default.
• W4313251268 cites W2903893784 @default.
• W4313251268 cites W2912328696 @default.
• W4313251268 cites W2978724020 @default.
• W4313251268 cites W2982250586 @default.
• W4313251268 cites W2989563826 @default.
• W4313251268 cites W3013764433 @default.
• W4313251268 cites W3024111705 @default.
• W4313251268 cites W3087353732 @default.
• W4313251268 cites W30969460 @default.
• W4313251268 cites W3209871456 @default.
• W4313251268 cites W4200269804 @default.
• W4313251268 cites W4210989661 @default.
• W4313251268 cites W4211093028 @default.
• W4313251268 cites W4211145066 @default.
• W4313251268 cites W4213422380 @default.
• W4313251268 cites W4225873156 @default.
• W4313251268 cites W4229929923 @default.
• W4313251268 cites W4237142507 @default.
• W4313251268 cites W4305040308 @default.
• W4313251268 doi "https://doi.org/10.1073/pnas.2217732120" @default.
• W4313251268 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36574686" @default.
• W4313251268 hasPublicationYear "2022" @default.
• W4313251268 type Work @default.
• W4313251268 citedByCount "6" @default.
• W4313251268 countsByYear W43132512682023 @default.
• W4313251268 crossrefType "journal-article" @default.
• W4313251268 hasAuthorship W4313251268A5018263796 @default.
• W4313251268 hasAuthorship W4313251268A5035289238 @default.
• W4313251268 hasAuthorship W4313251268A5037681035 @default.
• W4313251268 hasAuthorship W4313251268A5047013622 @default.
• W4313251268 hasAuthorship W4313251268A5074307523 @default.
• W4313251268 hasBestOaLocation W43132512681 @default.
• W4313251268 hasConcept C165901193 @default.
• W4313251268 hasConcept C2776225656 @default.
• W4313251268 hasConcept C2776863245 @default.
• W4313251268 hasConcept C2778359929 @default.
• W4313251268 hasConcept C2778491710 @default.
• W4313251268 hasConcept C2779744950 @default.
• W4313251268 hasConcept C2781355164 @default.
• W4313251268 hasConcept C54355233 @default.
• W4313251268 hasConcept C86803240 @default.
• W4313251268 hasConcept C90856448 @default.
• W4313251268 hasConceptScore W4313251268C165901193 @default.
• W4313251268 hasConceptScore W4313251268C2776225656 @default.
• W4313251268 hasConceptScore W4313251268C2776863245 @default.
• W4313251268 hasConceptScore W4313251268C2778359929 @default.
• W4313251268 hasConceptScore W4313251268C2778491710 @default.
• W4313251268 hasConceptScore W4313251268C2779744950 @default.

• next