Matches in SemOpenAlex for { <https://semopenalex.org/work/W3046669191> ?p ?o ?g. }
- W3046669191 endingPage "105504" @default.
- W3046669191 startingPage "105504" @default.
- W3046669191 abstract "4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is the second enzyme of the tyrosine catabolic pathway. Its physiological function is to catalyze the conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid, which displays different physiological effects in mammals and plants. Insights on the selective inhibition of human HPPD (hHPPD) by triketone inhibitors were furnished by the integrated application of molecular simulation and biological testing. The binding free energy of hHPPD and inhibitors was obtained through molecular dynamics (MD) simulations, and the result was in agreement with the inhibition experiment in vitro. The binding free energy contribution demonstrated that the formation of hHPPD-inhibitor complexes was mainly driven by van der Waals energy. Ser226, Asn241, Gln265, Phe336, Phe359 and Phe364 made great contributions to binding affinities of all the systems. Among the residues involved in the interaction between nitisinone (NTBC) and hHPPD, Tyr221 and Leu224, whose mutation into Ala caused significant decrease of NTBC binding ability, were two key residues in determining the selective binding affinity of inhibitor and hHPPD. This work provides valuable theoretical basis for rational design of highly selective inhibitors targeting hHPPD." @default.
- W3046669191 created "2020-08-07" @default.
- W3046669191 creator A5007217510 @default.
- W3046669191 creator A5024385167 @default.
- W3046669191 creator A5029877998 @default.
- W3046669191 creator A5034106927 @default.
- W3046669191 creator A5050108568 @default.
- W3046669191 creator A5060684356 @default.
- W3046669191 creator A5071222102 @default.
- W3046669191 date "2020-11-01" @default.
- W3046669191 modified "2023-10-03" @default.
- W3046669191 title "Identification of key residues determining the binding specificity of human 4-hydroxyphenylpyruvate dioxygenase" @default.
- W3046669191 cites W2002062654 @default.
- W3046669191 cites W2009416721 @default.
- W3046669191 cites W2011783601 @default.
- W3046669191 cites W2025323800 @default.
- W3046669191 cites W2025406292 @default.
- W3046669191 cites W2040096126 @default.
- W3046669191 cites W2054157673 @default.
- W3046669191 cites W2080192440 @default.
- W3046669191 cites W2085731957 @default.
- W3046669191 cites W2095569747 @default.
- W3046669191 cites W2127733149 @default.
- W3046669191 cites W2128586767 @default.
- W3046669191 cites W2133648941 @default.
- W3046669191 cites W2134308659 @default.
- W3046669191 cites W2174169848 @default.
- W3046669191 cites W2261015472 @default.
- W3046669191 cites W2288550151 @default.
- W3046669191 cites W2317607221 @default.
- W3046669191 cites W2321667681 @default.
- W3046669191 cites W2554161387 @default.
- W3046669191 cites W2580134572 @default.
- W3046669191 cites W2760647541 @default.
- W3046669191 cites W2886199156 @default.
- W3046669191 cites W2910626703 @default.
- W3046669191 cites W2922252162 @default.
- W3046669191 cites W2959300394 @default.
- W3046669191 cites W2962938003 @default.
- W3046669191 cites W2969526619 @default.
- W3046669191 cites W2974059633 @default.
- W3046669191 cites W2978413822 @default.
- W3046669191 cites W2980289225 @default.
- W3046669191 cites W3008797869 @default.
- W3046669191 cites W3009210895 @default.
- W3046669191 cites W3009244409 @default.
- W3046669191 cites W3013348398 @default.
- W3046669191 cites W4249645390 @default.
- W3046669191 doi "https://doi.org/10.1016/j.ejps.2020.105504" @default.
- W3046669191 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32750420" @default.
- W3046669191 hasPublicationYear "2020" @default.
- W3046669191 type Work @default.
- W3046669191 sameAs 3046669191 @default.
- W3046669191 citedByCount "6" @default.
- W3046669191 countsByYear W30466691912021 @default.
- W3046669191 countsByYear W30466691912022 @default.
- W3046669191 crossrefType "journal-article" @default.
- W3046669191 hasAuthorship W3046669191A5007217510 @default.
- W3046669191 hasAuthorship W3046669191A5024385167 @default.
- W3046669191 hasAuthorship W3046669191A5029877998 @default.
- W3046669191 hasAuthorship W3046669191A5034106927 @default.
- W3046669191 hasAuthorship W3046669191A5050108568 @default.
- W3046669191 hasAuthorship W3046669191A5060684356 @default.
- W3046669191 hasAuthorship W3046669191A5071222102 @default.
- W3046669191 hasConcept C107824862 @default.
- W3046669191 hasConcept C170493617 @default.
- W3046669191 hasConcept C181199279 @default.
- W3046669191 hasConcept C185592680 @default.
- W3046669191 hasConcept C2776255415 @default.
- W3046669191 hasConcept C2776834422 @default.
- W3046669191 hasConcept C3018795828 @default.
- W3046669191 hasConcept C53105671 @default.
- W3046669191 hasConcept C54355233 @default.
- W3046669191 hasConcept C55493867 @default.
- W3046669191 hasConcept C71240020 @default.
- W3046669191 hasConcept C86803240 @default.
- W3046669191 hasConceptScore W3046669191C107824862 @default.
- W3046669191 hasConceptScore W3046669191C170493617 @default.
- W3046669191 hasConceptScore W3046669191C181199279 @default.
- W3046669191 hasConceptScore W3046669191C185592680 @default.
- W3046669191 hasConceptScore W3046669191C2776255415 @default.
- W3046669191 hasConceptScore W3046669191C2776834422 @default.
- W3046669191 hasConceptScore W3046669191C3018795828 @default.
- W3046669191 hasConceptScore W3046669191C53105671 @default.
- W3046669191 hasConceptScore W3046669191C54355233 @default.
- W3046669191 hasConceptScore W3046669191C55493867 @default.
- W3046669191 hasConceptScore W3046669191C71240020 @default.
- W3046669191 hasConceptScore W3046669191C86803240 @default.
- W3046669191 hasFunder F4320321001 @default.
- W3046669191 hasFunder F4320323085 @default.
- W3046669191 hasLocation W30466691911 @default.
- W3046669191 hasOpenAccess W3046669191 @default.
- W3046669191 hasPrimaryLocation W30466691911 @default.
- W3046669191 hasRelatedWork W1971387475 @default.
- W3046669191 hasRelatedWork W2020980248 @default.
- W3046669191 hasRelatedWork W2067112397 @default.
- W3046669191 hasRelatedWork W2126100091 @default.
- W3046669191 hasRelatedWork W2278690205 @default.