FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2058552482> ?p ?o ?g. }

• W2058552482 endingPage "727" @default.
• W2058552482 startingPage "722" @default.
• W2058552482 abstract "Context: A steroidal alkaloid, 4-acetoxy-plakinamine B (4APB), is a recently discovered marine natural product with inhibitory effect against acetylcholinesterase (AChE), but its mechanism of interaction with the enzyme remains to be elucidated.Objective: The main objective was to study molecular binding mode of the compound, its interactions with catalytic subsites and molecular mechanism behind its significant inhibitory effect.Materials and methods: All possible interactions of ligands in the binding sites were analyzed using FRED 2.1 and the OMEGA pre-generated multi-conformer library.Results: Dipole–dipole interactions were observed between the secondary amino group of 4APB and Ser200 at a distance of 3.91 Å and also with Gly117 and Gly118. A further dipole–dipole interaction was between Arg289 and the heterocyclic nitrogen. Hydrogen bonding interactions were observed between Tyr130 and secondary amino and C-4 acetyl groups as well as between heterocyclic nitrogen and Phe288 at a distance of 3.04 Å. Hydrophobic interactions were evident between rings C/D of 4APB and with Phe288, Phe330 and Phe331. The computational studies revealed 4APB’s critical molecular interaction with amino acids of peripheral active (PAS) and anionic (AS) subsites.Discussion: Our data provided molecular evidence for the mixed competitive inhibitory effect of 4APB. For lead optimization, structural insights revealed the N-methyl group of 4APB could be replaced by NH2 moiety to generate a more favorable hydrogen bonding with Glu199. A polar group insertion such as NH2 or OH at certain sites of the 4APB skeleton is also recommended.Conclusion: These computational insights explained the mixed-competitive enzyme kinetic behavior of 4APB. This study outlines a strategy for designing novel derivatives of 4APB with potentially better AChE inhibitory activities through interaction at the PAS and AS sites." @default.
• W2058552482 created "2016-06-24" @default.
• W2058552482 creator A5001480595 @default.
• W2058552482 creator A5004704081 @default.
• W2058552482 creator A5010899653 @default.
• W2058552482 creator A5040488781 @default.
• W2058552482 creator A5050614530 @default.
• W2058552482 creator A5060754442 @default.
• W2058552482 creator A5071533103 @default.
• W2058552482 creator A5078586967 @default.
• W2058552482 creator A5089815918 @default.
• W2058552482 date "2013-04-09" @default.
• W2058552482 modified "2023-09-24" @default.
• W2058552482 title "Molecular interactions of 4-acetoxy-plakinamine B with peripheral anionic and other catalytic subsites of the aromatic gorge of acetylcholinesterase: Computational and structural insights" @default.
• W2058552482 cites W1525243744 @default.
• W2058552482 cites W1965894713 @default.
• W2058552482 cites W1971748623 @default.
• W2058552482 cites W1996226258 @default.
• W2058552482 cites W1997614802 @default.
• W2058552482 cites W1999391438 @default.
• W2058552482 cites W2004634185 @default.
• W2058552482 cites W2015331537 @default.
• W2058552482 cites W2022997414 @default.
• W2058552482 cites W2039895159 @default.
• W2058552482 cites W2046496198 @default.
• W2058552482 cites W2048302866 @default.
• W2058552482 cites W2048512374 @default.
• W2058552482 cites W2070466025 @default.
• W2058552482 cites W2074668510 @default.
• W2058552482 cites W2082043064 @default.
• W2058552482 cites W2085438248 @default.
• W2058552482 cites W2086758152 @default.
• W2058552482 doi "https://doi.org/10.3109/13880209.2013.764329" @default.
• W2058552482 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23570516" @default.
• W2058552482 hasPublicationYear "2013" @default.
• W2058552482 type Work @default.
• W2058552482 sameAs 2058552482 @default.
• W2058552482 citedByCount "11" @default.
• W2058552482 countsByYear W20585524822012 @default.
• W2058552482 countsByYear W20585524822014 @default.
• W2058552482 countsByYear W20585524822015 @default.
• W2058552482 countsByYear W20585524822016 @default.
• W2058552482 countsByYear W20585524822017 @default.
• W2058552482 countsByYear W20585524822019 @default.
• W2058552482 countsByYear W20585524822021 @default.
• W2058552482 crossrefType "journal-article" @default.
• W2058552482 hasAuthorship W2058552482A5001480595 @default.
• W2058552482 hasAuthorship W2058552482A5004704081 @default.
• W2058552482 hasAuthorship W2058552482A5010899653 @default.
• W2058552482 hasAuthorship W2058552482A5040488781 @default.
• W2058552482 hasAuthorship W2058552482A5050614530 @default.
• W2058552482 hasAuthorship W2058552482A5060754442 @default.
• W2058552482 hasAuthorship W2058552482A5071533103 @default.
• W2058552482 hasAuthorship W2058552482A5078586967 @default.
• W2058552482 hasAuthorship W2058552482A5089815918 @default.
• W2058552482 hasBestOaLocation W20585524821 @default.
• W2058552482 hasConcept C112887158 @default.
• W2058552482 hasConcept C137277065 @default.
• W2058552482 hasConcept C147597530 @default.
• W2058552482 hasConcept C151730666 @default.
• W2058552482 hasConcept C161790260 @default.
• W2058552482 hasConcept C178790620 @default.
• W2058552482 hasConcept C181199279 @default.
• W2058552482 hasConcept C185592680 @default.
• W2058552482 hasConcept C18705241 @default.
• W2058552482 hasConcept C2776568683 @default.
• W2058552482 hasConcept C2778565081 @default.
• W2058552482 hasConcept C2778816929 @default.
• W2058552482 hasConcept C2779343474 @default.
• W2058552482 hasConcept C2781311116 @default.
• W2058552482 hasConcept C32909587 @default.
• W2058552482 hasConcept C41183919 @default.
• W2058552482 hasConcept C71240020 @default.
• W2058552482 hasConcept C86803240 @default.
• W2058552482 hasConceptScore W2058552482C112887158 @default.
• W2058552482 hasConceptScore W2058552482C137277065 @default.
• W2058552482 hasConceptScore W2058552482C147597530 @default.
• W2058552482 hasConceptScore W2058552482C151730666 @default.
• W2058552482 hasConceptScore W2058552482C161790260 @default.
• W2058552482 hasConceptScore W2058552482C178790620 @default.
• W2058552482 hasConceptScore W2058552482C181199279 @default.
• W2058552482 hasConceptScore W2058552482C185592680 @default.
• W2058552482 hasConceptScore W2058552482C18705241 @default.
• W2058552482 hasConceptScore W2058552482C2776568683 @default.
• W2058552482 hasConceptScore W2058552482C2778565081 @default.
• W2058552482 hasConceptScore W2058552482C2778816929 @default.
• W2058552482 hasConceptScore W2058552482C2779343474 @default.
• W2058552482 hasConceptScore W2058552482C2781311116 @default.
• W2058552482 hasConceptScore W2058552482C32909587 @default.
• W2058552482 hasConceptScore W2058552482C41183919 @default.
• W2058552482 hasConceptScore W2058552482C71240020 @default.
• W2058552482 hasConceptScore W2058552482C86803240 @default.
• W2058552482 hasIssue "6" @default.
• W2058552482 hasLocation W20585524821 @default.
• W2058552482 hasLocation W20585524822 @default.
• W2058552482 hasOpenAccess W2058552482 @default.
• W2058552482 hasPrimaryLocation W20585524821 @default.
• W2058552482 hasRelatedWork W1804425206 @default.

• next