FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2087249553> ?p ?o ?g. }

• W2087249553 endingPage "677" @default.
• W2087249553 startingPage "668" @default.
• W2087249553 abstract "This study demonstrates that benzo[g]chrysene-11,12-dihydrodiol (B[g]C-11,12-dihydrodiol) derived from the fjord-region parent hydrocarbon B[g]C is oxidized by rat AKR1C9 with a k c a t/ K m 100 times greater than that observed with the commonly studied bay-region benzo[ a]pyrene-7,8-dihydrodiol (B[a]P-7,8-dihydrodiol). Conversely, despite its strikingly similar structure to B[ g]C-11,12-dihydrodiol, benzo[ c]phenanthrene-3,4-dihydrodiol (B[ c]Ph-3,4-dihydrodiol) is consumed by AKR1C9 at sluggish rates comparable to those observed with B[ a]P-7,8-dihydrodiol. CD spectroscopy revealed that only the (+)-B[ g]C-11,12-dihydrodiol stereoisomer was oxidized, while AKR1C9 oxidized both stereoisomers of B[a]P-7,8-dihydrodiol and B[ c]Ph-3,4-dihydrodiol. The (+)- S, S- and (-)- R, R-stereoisomers of B[g]C-11,12-dihydrodiol were purified by chiral RP-HPLC. The 11 S,12 S-stereoisomer was oxidized at the same rate as the racemate. The 11 R,12 R-stereoisomer did not act as an inhibitor to AKR1C9, indicating that the (-)- R, R-stereoisomer was excluded from the active site. To understand the basis of stereochemical preference, we screened alanine-scanning mutants of active site residues of AKR1C9. These studies revealed that in comparison to the wild type, F129A, W227A, and Y310A enabled the oxidation of both the B[g]C-11 S,12 S-dihydrodiol and the B[g]C-11 R,12 R-dihydrodiol. Molecular modeling revealed that unlike B[a]P-7,8-dihydrodiol and B[ c]Ph-3,4-dihydrodiol, B[g]C-11,12-dihydrodiol enantiomers are significantly bent out of plane. As a consequence, the (-)- R, R-stereoisomer was prevented from binding to the active site because of unfavorable interactions with F129, W227, or Y310. Additionally, LC/MS validated that the product of the reaction of B[g]C-11,12-dihydrodiol oxidation catalyzed by AKR1C9 was B[g]C-11,12-dione, which was trapped in vitro with the nucleophile 2-mercaptoethanol. The similarity between rates of trans-dihydrodiol oxidation by the rat and human liver specific AKRs (AKR1C9 and AKR1C4) implicate these enzymes in hepatocarcinogenesis in rats observed with the fjord-region PAH." @default.
• W2087249553 created "2016-06-24" @default.
• W2087249553 creator A5012263259 @default.
• W2087249553 creator A5018986737 @default.
• W2087249553 creator A5024335537 @default.
• W2087249553 creator A5036631157 @default.
• W2087249553 creator A5059737908 @default.
• W2087249553 creator A5079384190 @default.
• W2087249553 date "2008-02-06" @default.
• W2087249553 modified "2023-09-26" @default.
• W2087249553 title "<i>Fjord-</i>region Benzo[<i>g</i>]chrysene-11,12-dihydrodiol and Benzo[<i>c</i>]phenanthrene-3,4-dihydrodiol as Substrates for Rat Liver Dihydrodiol Dehydrogenase (AKR1C9): Structural Basis for Stereochemical Preference" @default.
• W2087249553 cites W1495618944 @default.
• W2087249553 cites W1534343559 @default.
• W2087249553 cites W1881840670 @default.
• W2087249553 cites W1972850783 @default.
• W2087249553 cites W1974760742 @default.
• W2087249553 cites W1982198624 @default.
• W2087249553 cites W1983714144 @default.
• W2087249553 cites W1985477010 @default.
• W2087249553 cites W1986906463 @default.
• W2087249553 cites W1987573118 @default.
• W2087249553 cites W1990934241 @default.
• W2087249553 cites W2003517116 @default.
• W2087249553 cites W2008618763 @default.
• W2087249553 cites W2019242355 @default.
• W2087249553 cites W2019605110 @default.
• W2087249553 cites W2021750867 @default.
• W2087249553 cites W2031109095 @default.
• W2087249553 cites W2031560521 @default.
• W2087249553 cites W2036453168 @default.
• W2087249553 cites W2036632136 @default.
• W2087249553 cites W2045928316 @default.
• W2087249553 cites W2046638467 @default.
• W2087249553 cites W2055578842 @default.
• W2087249553 cites W2060603106 @default.
• W2087249553 cites W2062949189 @default.
• W2087249553 cites W2065758000 @default.
• W2087249553 cites W2083470544 @default.
• W2087249553 cites W2084994361 @default.
• W2087249553 cites W2086592404 @default.
• W2087249553 cites W2088193717 @default.
• W2087249553 cites W2091231452 @default.
• W2087249553 cites W2101324933 @default.
• W2087249553 cites W2113357785 @default.
• W2087249553 cites W2131723216 @default.
• W2087249553 cites W2156865675 @default.
• W2087249553 cites W2159615011 @default.
• W2087249553 cites W2328757059 @default.
• W2087249553 cites W289471989 @default.
• W2087249553 doi "https://doi.org/10.1021/tx7003695" @default.
• W2087249553 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2440589" @default.
• W2087249553 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18251511" @default.
• W2087249553 hasPublicationYear "2008" @default.
• W2087249553 type Work @default.
• W2087249553 sameAs 2087249553 @default.
• W2087249553 citedByCount "2" @default.
• W2087249553 countsByYear W20872495532012 @default.
• W2087249553 crossrefType "journal-article" @default.
• W2087249553 hasAuthorship W2087249553A5012263259 @default.
• W2087249553 hasAuthorship W2087249553A5018986737 @default.
• W2087249553 hasAuthorship W2087249553A5024335537 @default.
• W2087249553 hasAuthorship W2087249553A5036631157 @default.
• W2087249553 hasAuthorship W2087249553A5059737908 @default.
• W2087249553 hasAuthorship W2087249553A5079384190 @default.
• W2087249553 hasBestOaLocation W20872495532 @default.
• W2087249553 hasConcept C178790620 @default.
• W2087249553 hasConcept C181199279 @default.
• W2087249553 hasConcept C185592680 @default.
• W2087249553 hasConcept C2775959351 @default.
• W2087249553 hasConcept C2776891815 @default.
• W2087249553 hasConcept C2777538855 @default.
• W2087249553 hasConcept C2778951431 @default.
• W2087249553 hasConcept C27881333 @default.
• W2087249553 hasConcept C55493867 @default.
• W2087249553 hasConcept C71240020 @default.
• W2087249553 hasConceptScore W2087249553C178790620 @default.
• W2087249553 hasConceptScore W2087249553C181199279 @default.
• W2087249553 hasConceptScore W2087249553C185592680 @default.
• W2087249553 hasConceptScore W2087249553C2775959351 @default.
• W2087249553 hasConceptScore W2087249553C2776891815 @default.
• W2087249553 hasConceptScore W2087249553C2777538855 @default.
• W2087249553 hasConceptScore W2087249553C2778951431 @default.
• W2087249553 hasConceptScore W2087249553C27881333 @default.
• W2087249553 hasConceptScore W2087249553C55493867 @default.
• W2087249553 hasConceptScore W2087249553C71240020 @default.
• W2087249553 hasIssue "3" @default.
• W2087249553 hasLocation W20872495531 @default.
• W2087249553 hasLocation W20872495532 @default.
• W2087249553 hasLocation W20872495533 @default.
• W2087249553 hasLocation W20872495534 @default.
• W2087249553 hasOpenAccess W2087249553 @default.
• W2087249553 hasPrimaryLocation W20872495531 @default.
• W2087249553 hasRelatedWork W1570500846 @default.
• W2087249553 hasRelatedWork W1967777883 @default.
• W2087249553 hasRelatedWork W1984696778 @default.
• W2087249553 hasRelatedWork W1987887169 @default.
• W2087249553 hasRelatedWork W2000400614 @default.
• W2087249553 hasRelatedWork W2027918953 @default.

• next