FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3204241402> ?p ?o ?g. }

• W3204241402 abstract "Abstract A clinically relevant inhibitor for Heptosyltransferase I (HepI) has been sought after for many years and while many have designed novel small-molecule inhibitors, these compounds lack the bioavailability and potency necessary for therapeutic use. Extensive characterization of the HepI protein has provided valuable insight into the dynamic motions necessary for catalysis that could be targeted for inhibition. With the help of molecular dynamic simulations, aminoglycoside antibiotics were shown to be putative inhibitors for HepI and in this study, they were experimentally determined to be the first in-class nanomolar inhibitors of HepI with the best inhibitor demonstrating a K i of 600 +/- 90 nM. Detailed kinetic analyses were performed to determine the mechanism of inhibition while circular dichroism spectroscopy, intrinsic tryptophan fluorescence, docking, and MD simulations were used to corroborate kinetic experimental findings. Kinetic analysis methods include Lineweaver-Burk, Dixon, Cornish-Bowden and Mixed-Model of Inhibition which allowed for unambiguous assignment of inhibition mechanism for each inhibitor. In this study, we show that neomycin and kanamycin b are competitive inhibitors against the sugar acceptor substrate while tobramycin exhibits a mixed inhibitory effect and streptomycin is non-competitive. MD simulations also allowed us to suggest that the inhibitors bind tightly and inhibit catalytic dynamics due to a major desolvation penalty of the enzyme active site. While aminoglycosides have long been known as a class of potent antibiotics, they also have been scientifically shown to impact cell membrane stability, and we propose that inhibition of HepI contributes to this effect by disrupting lipopolysaccharide biosynthesis." @default.
• W3204241402 created "2021-10-11" @default.
• W3204241402 creator A5004812000 @default.
• W3204241402 creator A5019188545 @default.
• W3204241402 creator A5019449054 @default.
• W3204241402 creator A5026508500 @default.
• W3204241402 creator A5043260507 @default.
• W3204241402 creator A5044529983 @default.
• W3204241402 creator A5054723613 @default.
• W3204241402 creator A5064100237 @default.
• W3204241402 creator A5065278513 @default.
• W3204241402 creator A5066445757 @default.
• W3204241402 creator A5084127002 @default.
• W3204241402 date "2021-10-04" @default.
• W3204241402 modified "2023-09-26" @default.
• W3204241402 title "Discovery of Aminoglycosides as first in class, nanomolar inhibitors of Heptosyltransferase I" @default.
• W3204241402 cites W111685663 @default.
• W3204241402 cites W1968984443 @default.
• W3204241402 cites W1975447903 @default.
• W3204241402 cites W1976499671 @default.
• W3204241402 cites W1985588649 @default.
• W3204241402 cites W2031168104 @default.
• W3204241402 cites W2035266068 @default.
• W3204241402 cites W2036140802 @default.
• W3204241402 cites W2037535298 @default.
• W3204241402 cites W2045683699 @default.
• W3204241402 cites W2057477511 @default.
• W3204241402 cites W2059013449 @default.
• W3204241402 cites W2059540567 @default.
• W3204241402 cites W2060534420 @default.
• W3204241402 cites W2075814736 @default.
• W3204241402 cites W2081693079 @default.
• W3204241402 cites W2091432870 @default.
• W3204241402 cites W2093381148 @default.
• W3204241402 cites W2095719702 @default.
• W3204241402 cites W2106383417 @default.
• W3204241402 cites W2108638835 @default.
• W3204241402 cites W2129153475 @default.
• W3204241402 cites W2144288821 @default.
• W3204241402 cites W2147993766 @default.
• W3204241402 cites W2171268876 @default.
• W3204241402 cites W2177149876 @default.
• W3204241402 cites W2316777574 @default.
• W3204241402 cites W2327581403 @default.
• W3204241402 cites W2330799739 @default.
• W3204241402 cites W2416290591 @default.
• W3204241402 cites W2513677890 @default.
• W3204241402 cites W2578503505 @default.
• W3204241402 cites W2767158766 @default.
• W3204241402 cites W2783855936 @default.
• W3204241402 cites W2794330111 @default.
• W3204241402 cites W2885806560 @default.
• W3204241402 cites W2912818999 @default.
• W3204241402 cites W2954094311 @default.
• W3204241402 cites W3005408528 @default.
• W3204241402 cites W3158834189 @default.
• W3204241402 cites W3167485199 @default.
• W3204241402 cites W4234317413 @default.
• W3204241402 cites W4236273750 @default.
• W3204241402 cites W4236997449 @default.
• W3204241402 cites W4240187346 @default.
• W3204241402 cites W4241111610 @default.
• W3204241402 cites W4246043393 @default.
• W3204241402 cites W4249193413 @default.
• W3204241402 cites W4249304889 @default.
• W3204241402 doi "https://doi.org/10.1101/2021.10.03.462930" @default.
• W3204241402 hasPublicationYear "2021" @default.
• W3204241402 type Work @default.
• W3204241402 sameAs 3204241402 @default.
• W3204241402 citedByCount "0" @default.
• W3204241402 crossrefType "posted-content" @default.
• W3204241402 hasAuthorship W3204241402A5004812000 @default.
• W3204241402 hasAuthorship W3204241402A5019188545 @default.
• W3204241402 hasAuthorship W3204241402A5019449054 @default.
• W3204241402 hasAuthorship W3204241402A5026508500 @default.
• W3204241402 hasAuthorship W3204241402A5043260507 @default.
• W3204241402 hasAuthorship W3204241402A5044529983 @default.
• W3204241402 hasAuthorship W3204241402A5054723613 @default.
• W3204241402 hasAuthorship W3204241402A5064100237 @default.
• W3204241402 hasAuthorship W3204241402A5065278513 @default.
• W3204241402 hasAuthorship W3204241402A5066445757 @default.
• W3204241402 hasAuthorship W3204241402A5084127002 @default.
• W3204241402 hasBestOaLocation W32042414021 @default.
• W3204241402 hasConcept C12554922 @default.
• W3204241402 hasConcept C150757390 @default.
• W3204241402 hasConcept C159110408 @default.
• W3204241402 hasConcept C181199279 @default.
• W3204241402 hasConcept C185592680 @default.
• W3204241402 hasConcept C2777787772 @default.
• W3204241402 hasConcept C41685203 @default.
• W3204241402 hasConcept C501593827 @default.
• W3204241402 hasConcept C55493867 @default.
• W3204241402 hasConcept C71240020 @default.
• W3204241402 hasConcept C71924100 @default.
• W3204241402 hasConcept C86803240 @default.
• W3204241402 hasConceptScore W3204241402C12554922 @default.
• W3204241402 hasConceptScore W3204241402C150757390 @default.
• W3204241402 hasConceptScore W3204241402C159110408 @default.
• W3204241402 hasConceptScore W3204241402C181199279 @default.
• W3204241402 hasConceptScore W3204241402C185592680 @default.

• next