InChI=1S/C20H32O4/c21-18-13-11-9-7-5-3-1-2-4-6-8-10-12-15-19(22)16-14-17-20(23)24/h2-5,8,10,12,15,19,21-22H,1,6-7,9,11,13-14,16-18H2,(H,23,24)/p-1/b4-2-,5-3-,10-8-,15-12+ |
IWYJGYZCHKEPCK-DHYYJNSCSA-M |
C(=O)([O-])CCCC(/C=C/C=C\C/C=C\C/C=C\CCCCCO)O |
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(6E,8Z,11Z,14Z)-5,20-dihydroxyicosa-6,8,11,14-tetraenoate
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(6E,8Z,11Z,14Z)-5,20-dihydroxyicosatetraenoate
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ChEBI
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5,20-dihydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate
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UniProt
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5,20-dihydroxy-6E,8Z,11Z,14Z-eicosatetraenoate
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SUBMITTER
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5,20-dihydroxy-6E,8Z,11Z,14Z-icosatetraenoate
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ChEBI
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Kalsotra A, Turman CM, Kikuta Y, Strobel HW (2004) Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids. Toxicology and applied pharmacology 199, 295-304 (Source: SUBMITTER) [PubMed:15364545] [show Abstract] We previously reported the cDNA cloning of a new CYP4F isoform, CYP4F11. In the present study, we have expressed CYP4F11 in Saccharomyces cerevisiae and examined its catalytic properties towards endogenous eicosanoids as well as some clinically relevant drugs. CYP4F3A, also known as a leukotriene B4 omega-hydroxylase, was expressed in parallel for comparative purposes. Our results show that CYP4F11 has a very different substrate profile than CYP4F3A. CYP4F3A metabolized leukotriene B4, lipoxins A4 and B4, and hydroxyeicosatetraenoic acids (HETEs) much more efficiently than CYP4F11. On the other hand, CYP4F11 was a better catalyst than CYP4F3A for many drugs such as erythromycin, benzphetamine, ethylmorphine, chlorpromazine, and imipramine. Erythromycin was the most efficient substrate for CYP4F11, with a Km of 125 microM and Vmax of 830 pmol min(-1) nmol(-1) P450. Structural homology modeling of the two proteins revealed some interesting differences in the substrate access channel including substrate recognition site 2 (SRS2). The model of CYP4F11 presents a more open access channel that may explain the ability to metabolize large molecules like erythromycin. Also, some wide variations in residue size, charge, and hydrophobicity in the FG loop region may contribute to differences in substrate specificity and activity between CYP4F3A and CYP4F11. | Kikuta Y, Kusunose E, Sumimoto H, Mizukami Y, Takeshige K, Sakaki T, Yabusaki Y, Kusunose M (1998) Purification and characterization of recombinant human neutrophil leukotriene B4 omega-hydroxylase (cytochrome P450 4F3). Archives of biochemistry and biophysics 355, 201-205 (Source: SUBMITTER) [PubMed:9675028] [show Abstract] Recombinant human neutrophil leukotriene B4 (LTB4) omega-hydroxylase (cytochrome P450 4F3) has been purified to a specific content of 14. 8 nmol of P450/mg of protein from yeast cells. The purified enzyme was homogenous as judged from the SDS-PAGE, with an apparent molecular weight of 55 kDa. The enzyme catalyzed the omega-hydroxylation of LTB4 with a Km of 0.64 microM and Vmax of 34 nmol/min/nmol of P450 in the presence of rabbit hepatic NADPH-P450 reductase and cytochrome b5. Furthermore, various eicosanoids such as 20-hydroxy-LTB4, 6-trans-LTB4, lipoxin A4, lipoxin B4, 5-HETE and 12-HETE, and 12-hydroxy-stearate and 12-hydroxy-oleate were efficiently omega-hydroxylated, although their Km values were much higher than that of LTB4. In contrast, no activity was detected toward laurate, palmitate, arachidonate, 15-HETE, prostaglandin A1, and prostaglandin E1, all of which are excellent substrates for the CYP4A fatty acid omega-hydroxylases. This is the first time human neutrophil LTB4 omega-hydroxylase has been isolated in a highly purified state and characterized especially with respect to its substrate specificity. |
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