Matches in SemOpenAlex for { <https://semopenalex.org/work/W3039652313> ?p ?o ?g. }
- W3039652313 endingPage "115607" @default.
- W3039652313 startingPage "115607" @default.
- W3039652313 abstract "Research interest in the development of histone deacetylase 8 (HDAC8) activators has substantially increased since loss-of-function HDAC8 mutations were found in patients with Cornelia de Lange syndrome (CdLS). A series of N-acetylthioureas (e.g., TM-2-51) have been identified as HDAC8-selective activators, among others; however, their activation mechanisms remain elusive. Herein, we performed molecular dynamics (MD) simulations and fragment-centric topographical mapping (FCTM) to investigate the mechanism of HDAC8 activation. Our results revealed that improper binding of the coumarin group of fluorescent substrates leads to the “flipping out” of catalytic residue Y306, which reduces the enzymatic activity of HDAC8 towards fluorescent substrates. A pocket between the coumarin group of the substrate and thed catalytic residue Y306 was filled with the activator TM-2-51, which not only enhanced binding between HDAC8 and the fluorescent substrate complex but also stabilized Y306 in a catalytically active conformation. Based on this newly proposed substrate-dependent activation mechanism, we performed structure-based virtual screening and successfully identified low-molecular-weight scaffolds as new HDAC8 activators." @default.
- W3039652313 created "2020-07-10" @default.
- W3039652313 creator A5013861294 @default.
- W3039652313 creator A5038166418 @default.
- W3039652313 creator A5043891966 @default.
- W3039652313 creator A5063629758 @default.
- W3039652313 creator A5074773090 @default.
- W3039652313 creator A5087455824 @default.
- W3039652313 creator A5090815103 @default.
- W3039652313 date "2020-08-01" @default.
- W3039652313 modified "2023-10-02" @default.
- W3039652313 title "An in silico mechanistic insight into HDAC8 activation facilitates the discovery of new small-molecule activators" @default.
- W3039652313 cites W1532707293 @default.
- W3039652313 cites W1930265233 @default.
- W3039652313 cites W1973577140 @default.
- W3039652313 cites W1992584691 @default.
- W3039652313 cites W1999482446 @default.
- W3039652313 cites W2001704867 @default.
- W3039652313 cites W2007842741 @default.
- W3039652313 cites W2012085384 @default.
- W3039652313 cites W2018272903 @default.
- W3039652313 cites W2027592225 @default.
- W3039652313 cites W2030222772 @default.
- W3039652313 cites W2040439401 @default.
- W3039652313 cites W2041611469 @default.
- W3039652313 cites W2044216740 @default.
- W3039652313 cites W2056474673 @default.
- W3039652313 cites W2061360494 @default.
- W3039652313 cites W2065209644 @default.
- W3039652313 cites W2094383719 @default.
- W3039652313 cites W2103325328 @default.
- W3039652313 cites W2119707965 @default.
- W3039652313 cites W2126891469 @default.
- W3039652313 cites W2149263899 @default.
- W3039652313 cites W2157860216 @default.
- W3039652313 cites W2164806419 @default.
- W3039652313 cites W2165565773 @default.
- W3039652313 cites W2166496008 @default.
- W3039652313 cites W2166529463 @default.
- W3039652313 cites W2167021305 @default.
- W3039652313 cites W2168448928 @default.
- W3039652313 cites W2237717580 @default.
- W3039652313 cites W2271965344 @default.
- W3039652313 cites W2313116527 @default.
- W3039652313 cites W2403767926 @default.
- W3039652313 cites W2404280981 @default.
- W3039652313 cites W2476113726 @default.
- W3039652313 cites W2606303647 @default.
- W3039652313 cites W2737479905 @default.
- W3039652313 cites W2741487312 @default.
- W3039652313 doi "https://doi.org/10.1016/j.bmc.2020.115607" @default.
- W3039652313 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7373817" @default.
- W3039652313 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32690262" @default.
- W3039652313 hasPublicationYear "2020" @default.
- W3039652313 type Work @default.
- W3039652313 sameAs 3039652313 @default.
- W3039652313 citedByCount "4" @default.
- W3039652313 countsByYear W30396523132021 @default.
- W3039652313 countsByYear W30396523132022 @default.
- W3039652313 countsByYear W30396523132023 @default.
- W3039652313 crossrefType "journal-article" @default.
- W3039652313 hasAuthorship W3039652313A5013861294 @default.
- W3039652313 hasAuthorship W3039652313A5038166418 @default.
- W3039652313 hasAuthorship W3039652313A5043891966 @default.
- W3039652313 hasAuthorship W3039652313A5063629758 @default.
- W3039652313 hasAuthorship W3039652313A5074773090 @default.
- W3039652313 hasAuthorship W3039652313A5087455824 @default.
- W3039652313 hasAuthorship W3039652313A5090815103 @default.
- W3039652313 hasBestOaLocation W30396523132 @default.
- W3039652313 hasConcept C103697762 @default.
- W3039652313 hasConcept C104317684 @default.
- W3039652313 hasConcept C107824862 @default.
- W3039652313 hasConcept C119157956 @default.
- W3039652313 hasConcept C125209161 @default.
- W3039652313 hasConcept C12554922 @default.
- W3039652313 hasConcept C147597530 @default.
- W3039652313 hasConcept C159110408 @default.
- W3039652313 hasConcept C161624437 @default.
- W3039652313 hasConcept C181199279 @default.
- W3039652313 hasConcept C185592680 @default.
- W3039652313 hasConcept C25737173 @default.
- W3039652313 hasConcept C2775905019 @default.
- W3039652313 hasConcept C2778305200 @default.
- W3039652313 hasConcept C41183919 @default.
- W3039652313 hasConcept C41685203 @default.
- W3039652313 hasConcept C55493867 @default.
- W3039652313 hasConcept C59593255 @default.
- W3039652313 hasConcept C64927066 @default.
- W3039652313 hasConcept C71240020 @default.
- W3039652313 hasConcept C71924100 @default.
- W3039652313 hasConcept C74187038 @default.
- W3039652313 hasConcept C86803240 @default.
- W3039652313 hasConceptScore W3039652313C103697762 @default.
- W3039652313 hasConceptScore W3039652313C104317684 @default.
- W3039652313 hasConceptScore W3039652313C107824862 @default.
- W3039652313 hasConceptScore W3039652313C119157956 @default.
- W3039652313 hasConceptScore W3039652313C125209161 @default.
- W3039652313 hasConceptScore W3039652313C12554922 @default.