Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids

Toxicology and Applied Pharmacology
Auinash KalsotraHenry W Strobel

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 hydrophobicit...Continue Reading

Citations

Oct 9, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ying WangHenry W Strobel
Oct 21, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jordan C Bell, Henry W Strobel
Nov 28, 2012·Cellular Oncology (Dordrecht)·Nathalia Serna-MarquezEduardo Perez Salazar
Jun 7, 2013·Expert Opinion on Drug Metabolism & Toxicology·David C LambBin Zhao
Sep 6, 2007·Drug Metabolism Reviews·Mei-Hui HsuEric F Johnson
Sep 6, 2007·Drug Metabolism Reviews·Katarina Stark, F Peter Guengerich
Jan 22, 2013·Expert Opinion on Drug Metabolism & Toxicology·Vijayalakshmi Ravindranath, Henry W Strobel
Apr 7, 2011·Biochemical Pharmacology·Neha SehgalVijayalakshmi Ravindranath
Jan 19, 2010·Journal of Molecular Graphics & Modelling·Poornima GajendraraoKeun Woo Lee
Nov 26, 2009·Archives of Biochemistry and Biophysics·Zhongmei TangF Peter Guengerich
Jul 30, 2008·Archives of Biochemistry and Biophysics·Vandana HiraniJerome M Lasker
Nov 6, 2007·Biochimica Et Biophysica Acta·Yasushi KikutaHideo Ohkawa
Apr 10, 2007·Archives of Biochemistry and Biophysics·Auinash KalsotraHenry W Strobel
Feb 27, 2016·Molecular Pharmaceutics·Ahmed A El-Sherbeni, Ayman O S El-Kadi
Jun 14, 2008·The FEBS Journal·Katarina StarkF P Guengerich
Aug 24, 2006·Pharmacology & Therapeutics·Auinash Kalsotra, Henry W Strobel
Sep 27, 2005·Biochemical and Biophysical Research Communications·Auinash KalsotraHenry W Strobel
Sep 4, 2012·Asian Pacific Journal of Cancer Prevention : APJCP·Cindy BandalaE Lara-Padilla
May 29, 2012·Asian Pacific Journal of Cancer Prevention : APJCP·N Cárdenas-RodríguezE Floriano-Sánchez
Jul 16, 2015·Environmental Toxicology and Pharmacology·Sanda RavlićNevenka Bihari
Nov 15, 2011·Molecular Phylogenetics and Evolution·Nina L Kirischian, Joanna Y Wilson
Apr 6, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shotaro UeharaHiroshi Yamazaki
Sep 13, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Heta ShahNeeta Shrivastava
Dec 11, 2007·Journal of Lipid Research·Madhurima DharJerome M Lasker
May 13, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Scott Michaels, Michael Zhuo Wang
Nov 4, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yi JinChristopher J Patten
Sep 22, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Auinash KalsotraHenry W Strobel
Sep 5, 2019·International Journal of Molecular Sciences·Yazun Bashir Jarrar, Su-Jun Lee
Nov 26, 2010·The Journal of Veterinary Medical Science·Yasuhiro UnoHiroshi Yamazaki
Oct 4, 2018·Molecular Medicine Reports·Hyuk Soo EunKyung-Hee Kim
Oct 20, 2020·Frontiers in Neuroscience·Jun-Jie YuanQing-Wu Yang
May 4, 2021·Frontiers in Microbiology·James B Y H Behrendorff
Jun 18, 2021·Bioorganic & Medicinal Chemistry·Lisa Marie SchmitzStephan Lütz
Aug 30, 2005·Biochemical and Biophysical Research Communications·F Peter GuengerichCheryl J Bartleson

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