Cooperativity in oxidation reactions catalyzed by cytochrome P450 1A2: highly cooperative pyrene hydroxylation and multiphasic kinetics of ligand binding

The Journal of Biological Chemistry
Christal D SohlF Peter Guengerich

Abstract

Rabbit liver cytochrome P450 (P450) 1A2 was found to catalyze the 5,6-epoxidation of alpha-naphthoflavone (alphaNF), 1-hydroxylation of pyrene, and the subsequent 6-, 8-, and other hydroxylations of 1-hydroxy (OH) pyrene. Plots of steady-state rates of product formation versus substrate concentration were hyperbolic for alphaNF epoxidation but highly cooperative (Hill n coefficients of 2-4) for pyrene and 1-OH pyrene hydroxylation. When any of the three substrates (alphaNF, pyrene, 1-OH pyrene) were mixed with ferric P450 1A2 using stopped-flow methods, the changes in the heme Soret spectra were relatively slow and multiphasic. Changes in the fluorescence of all of the substrates were much faster, consistent with rapid initial binding to P450 1A2 in a manner that does not change the heme spectrum. For binding of pyrene to ferrous P450 1A2, the course of the spectra revealed sequential changes in opposite directions, consistent with P450 1A2 being involved in a series of transitions to explain the kinetic multiphasicity as opposed to multiple, slowly interconverting populations of enzyme undergoing the same event at different rates. Models of rabbit P450 1A2 based on a published crystal structure of a human P450 1A2-alphaNF comp...Continue Reading

References

May 15, 1978·Biochemical and Biophysical Research Communications·M K BueningA H Corney
Oct 1, 1977·Clinical Pharmacology and Therapeutics·J KapitulnikA H Conney
Oct 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·F J WiebelM J Coon
Feb 1, 1991·Annals of Epidemiology·D A Evans
Sep 1, 1990·Biomedical Chromatography : BMC·M A Alterman, A I Dowgii
Sep 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·L C QuattrochiR H Tukey
Mar 1, 1969·Analytical Biochemistry·G P FoustV Massey
Jun 25, 1982·Science·J M LaskerA H Conney
Jun 1, 1995·Canadian Journal of Microbiology·L LaunenM Moore
Jan 1, 1995·Chemical Research in Toxicology·E BauerF P Guengerich
Jan 14, 1997·Biochemistry·Y F UengF P Guengerich
Feb 7, 1997·The Journal of Biological Chemistry·A P KoleyF K Friedman
Aug 1, 1997·Nature Biotechnology·A ParikhF P Guengerich
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·G R Harlow, J R Halpert
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Oct 7, 1998·Chemical Research in Toxicology·T ShimadaF P Guengerich
May 23, 2000·Biochemistry·N A HoseaF P Guengerich
Jun 21, 2001·Chemical Research in Toxicology·F P Guengerich
Mar 20, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Matthew Hutzler, Timothy S Tracy
Oct 3, 2002·Journal of the American Chemical Society·Michael J DabrowskiWilliam M Atkins
Jun 26, 2003·Nucleic Acids Research·Torsten SchwedeManuel C Peitsch
Jul 16, 2003·Nature·Pamela A WilliamsHarren Jhoti
Mar 16, 2004·Environmental Research·Yong-Dae KimToshihiro Kawamoto
Jul 20, 2004·The Journal of Biological Chemistry·Jason K YanoEric F Johnson
Jul 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·Alexander W Schüttelkopf, Daan M F van Aalten
Aug 12, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Andrew WilliamsSimon E Ball
Aug 18, 2004·Biochemistry·F Peter GuengerichWilliam W Johnson
Jan 25, 2005·The Journal of Biological Chemistry·Chul-Ho YunF Peter Guengerich
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Donghak Kim, F Peter Guengerich
Apr 16, 2005·Annual Review of Pharmacology and Toxicology·William M Atkins
May 25, 2005·Archives of Biochemistry and Biophysics·Monica I JushchyshynLarry C Wienkers
Jul 20, 2005·Biochimica Et Biophysica Acta·Sharon M KellyNicholas C Price

❮ Previous
Next ❯

Citations

May 11, 2019·The Journal of Biological Chemistry·F Peter GuengerichMichael J Reddish
May 31, 2019·The Journal of Biological Chemistry·F Peter GuengerichThanh T N Phan
Dec 12, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Claudia N GenerauxMary F Paine
May 29, 2012·Journal of Computer-aided Molecular Design·Márton VassGyörgy M Keserű
Aug 21, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·F Peter Guengerich
Apr 14, 2010·The Journal of Biological Chemistry·Christal D Sohl, F Peter Guengerich
Dec 2, 2008·Expert Opinion on Drug Metabolism & Toxicology·Dmitri R Davydov, James R Halpert
Jul 16, 2008·Analytical and Bioanalytical Chemistry·Emre M Isin, F Peter Guengerich
Apr 8, 2011·The Journal of Biological Chemistry·Raku Shinkyo, F Peter Guengerich
Aug 8, 2015·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Tsutomu ShimadaMasayuki Komori
Jul 9, 2009·Journal of the American Chemical Society·Aaron T WrightBenjamin F Cravatt
Aug 8, 2015·Chemical Research in Toxicology·Kensaku KakimotoAkira Toriba
May 21, 2019·ACS Catalysis·F Peter Guengerich
Apr 26, 2016·The Journal of Physical Chemistry. a·Vaishali M PatilKrishnan Balasubramanian
May 28, 2019·Chemical Research in Toxicology·Zuzana JandovaChris Oostenbrink
Apr 26, 2012·Chemical Research in Toxicology·Slobodan Rendic, F Peter Guengerich
Sep 10, 2014·Biochemistry·Donghak KimF Peter Guengerich
Mar 13, 2014·Journal of Chemical Information and Modeling·Mian WangZhiqun Liang
Mar 11, 2008·Archives of Biochemistry and Biophysics·Emre M IsinF Peter Guengerich
Jun 27, 2009·Pharmacology & Therapeutics·Ilia G DenisovStephen G Sligar
May 25, 2010·Biochimica Et Biophysica Acta·F Peter GuengerichS Giovanna Salamanca-Pinzón

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.