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• W2550751504 endingPage "6980" @default.
• W2550751504 startingPage "6969" @default.
• W2550751504 abstract "Cytochrome P450 (CYP) 2J2 is the primary epoxygenase in the heart and is responsible for the epoxidation of arachidonic acid (AA), an ω-6 polyunsaturated fatty acid (PUFA), into anti-inflammatory epoxide metabolites. It also epoxidizes other PUFAs such as docosahexaenoic acid (DHA), linoleic acid (LA), and eicosapentaenoic acid (EPA). Herein, we have performed detailed thermodynamic and kinetic analyses to determine how DHA, LA, and EPA modulate the metabolism of AA by CYP2J2. We use the Nanodisc system to stabilize CYP2J2 and its redox partner, CYP reductase (CPR). We observe that DHA strongly inhibits CYP2J2-mediated AA metabolism, LA only moderately inhibits AA metabolism, and EPA exhibits insignificant inhibition. We also characterized the binding of these molecules using ebastine competitive binding assays and show that DHA binds significantly tighter to CYP2J2 than AA, EPA, or LA. Furthermore, we utilize a combined approach of molecular dynamics (MD) simulations and docking to predict key residues mediating the tight binding of DHA. We show that although all the tested fatty acids form similar contacts to the active site residues, the affinity of DHA for CYP2J2 is tighter because of the interaction of DHA with residues Arg-321, Thr-318, and Ser-493. To demonstrate the importance of these residues in binding, we mutated these residues to make two mutant variants, CYP2J2-T318A and CYP2J2-T318V/S493A. Both mutant variants showed weaker binding than the wild type (WT) to DHA and AA; DHA inhibition of AA was also mitigated in the mutants compared to the WT. Therefore, using a combined experimental and MD simulation approach, we establish that CYP2J2 inhibition of AA metabolism by DHA, EPA, and LA is asymmetric because of tighter binding of DHA to select residues in the active site." @default.
• W2550751504 created "2016-11-30" @default.
• W2550751504 creator A5026626873 @default.
• W2550751504 creator A5038017609 @default.
• W2550751504 creator A5081204904 @default.
• W2550751504 creator A5087810793 @default.
• W2550751504 date "2016-12-05" @default.
• W2550751504 modified "2023-10-09" @default.
• W2550751504 title "Asymmetric Binding and Metabolism of Polyunsaturated Fatty Acids (PUFAs) by CYP2J2 Epoxygenase" @default.
• W2550751504 cites W1005226196 @default.
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• W2550751504 cites W1532212858 @default.
• W2550751504 cites W1539392991 @default.
• W2550751504 cites W1605985146 @default.
• W2550751504 cites W1870633384 @default.
• W2550751504 cites W1882326031 @default.
• W2550751504 cites W1895462365 @default.
• W2550751504 cites W1910564820 @default.
• W2550751504 cites W1913730804 @default.
• W2550751504 cites W1942137053 @default.
• W2550751504 cites W1970620631 @default.
• W2550751504 cites W1972758026 @default.
• W2550751504 cites W1976499671 @default.
• W2550751504 cites W1982248155 @default.
• W2550751504 cites W1987542967 @default.
• W2550751504 cites W1992303064 @default.
• W2550751504 cites W1996856207 @default.
• W2550751504 cites W1997036567 @default.
• W2550751504 cites W2003639306 @default.
• W2550751504 cites W2004201056 @default.
• W2550751504 cites W2007180422 @default.
• W2550751504 cites W2008873477 @default.
• W2550751504 cites W2009718837 @default.
• W2550751504 cites W2010427019 @default.
• W2550751504 cites W2011609324 @default.
• W2550751504 cites W2012344270 @default.
• W2550751504 cites W2019501820 @default.
• W2550751504 cites W2021979829 @default.
• W2550751504 cites W2022097029 @default.
• W2550751504 cites W2025122196 @default.
• W2550751504 cites W2027978582 @default.
• W2550751504 cites W2029006437 @default.
• W2550751504 cites W2037113953 @default.
• W2550751504 cites W2038222125 @default.
• W2550751504 cites W2038434242 @default.
• W2550751504 cites W2038758364 @default.
• W2550751504 cites W2041345281 @default.
• W2550751504 cites W2047223968 @default.
• W2550751504 cites W2047319374 @default.
• W2550751504 cites W2055309018 @default.
• W2550751504 cites W2059476947 @default.
• W2550751504 cites W2060872117 @default.
• W2550751504 cites W2066414494 @default.
• W2550751504 cites W2067174909 @default.
• W2550751504 cites W2068378755 @default.
• W2550751504 cites W2070686757 @default.
• W2550751504 cites W2070753604 @default.
• W2550751504 cites W2072050417 @default.
• W2550751504 cites W2075560738 @default.
• W2550751504 cites W2094447236 @default.
• W2550751504 cites W2097685656 @default.
• W2550751504 cites W2105206504 @default.
• W2550751504 cites W2105953302 @default.
• W2550751504 cites W2106140689 @default.
• W2550751504 cites W2109225320 @default.
• W2550751504 cites W2113524447 @default.
• W2550751504 cites W2123869725 @default.
• W2550751504 cites W2132608896 @default.
• W2550751504 cites W2134967712 @default.
• W2550751504 cites W2139086060 @default.
• W2550751504 cites W2144476483 @default.
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• W2550751504 cites W2150981663 @default.
• W2550751504 cites W2157204944 @default.
• W2550751504 cites W2163545572 @default.
• W2550751504 cites W2166470238 @default.
• W2550751504 cites W2182635476 @default.
• W2550751504 cites W241512211 @default.
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• W2550751504 doi "https://doi.org/10.1021/acs.biochem.6b01037" @default.
• W2550751504 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5558443" @default.
• W2550751504 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27992998" @default.
• W2550751504 hasPublicationYear "2016" @default.
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