Homotropic cooperativity of monomeric cytochrome P450 3A4 in a nanoscale native bilayer environment

Archives of Biochemistry and Biophysics
Bradley J BaasStephen G Sligar

Abstract

Mechanistic studies of mammalian cytochrome P450s are often obscured by the phase heterogeneity of solubilized preparations of membrane enzymes. The various protein-protein aggregation states of microsomes, detergent solubilized cytochrome or a family of aqueous multimeric complexes can effect measured substrate binding events as well as subsequent steps in the reaction cycle. In addition, these P450 monooxygenases are normally found in a membrane environment and the bilayer composition and dynamics can also effect these catalytic steps. Here, we describe the structural and functional characterization of a homogeneous monomeric population of cytochrome P450 3A4 (CYP 3A4) in a soluble nanoscale membrane bilayer, or Nanodisc [Nano Lett. 2 (2002) 853]. Cytochrome P450 3A4:Nanodisc assemblies were formed and purified to yield a 1:1 ratio of CYP 3A4 to Nanodisc. Solution small angle X-ray scattering was used to structurally characterize this monomeric CYP 3A4 in the membrane bilayer. The purified CYP 3A4:Nanodiscs showed a heretofore undescribed high level of homotropic cooperativity in the binding of testosterone. Soluble CYP 3A4:Nanodisc retains its known function and shows prototypic hydroxylation of testosterone when driven by h...Continue Reading

References

Jun 7, 1976·Biochemical and Biophysical Research Communications·F LichtenbergerV Ullrich
Feb 1, 1989·Biophysical Journal·M C WienerJ F Nagle
Oct 15, 1973·Biochemical and Biophysical Research Communications·F F KadlubarD M Ziegler
May 1, 1973·Analytical Biochemistry·P W Holloway
Aug 15, 1993·Archives of Biochemistry and Biophysics·E M GillamF P Guengerich
Jan 14, 1997·Biochemistry·Y F UengF P Guengerich
Jun 2, 1998·Archives of Biochemistry and Biophysics·N A Hosea, F 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 22, 1998·Structure·C R Sanders, R S Prosser
Nov 4, 1998·Archives of Biochemistry and Biophysics·M L Shank-RetzlaffS G Sligar
May 20, 1999·Annual Review of Pharmacology and Toxicology·F P Guengerich
Dec 14, 1999·British Journal of Clinical Pharmacology·K E KenworthyJ B Houston
Mar 7, 2000·Journal of Computer-aided Molecular Design·F De RienzoP G De Benedetti
May 23, 2000·Biochemistry·N A HoseaF P Guengerich
Jun 22, 2000·The Journal of Biological Chemistry·J K YanoT L Poulos
Oct 29, 2000·Journal of Inorganic Biochemistry·P A WilliamsD E McRee
Jul 27, 2001·Current Drug Metabolism·W Tang, R A Stearns
Aug 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·S S FunariK Beyer
May 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Timothy H Bayburt, Stephen G Sligar
Dec 19, 2002·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J AndrewsJ B Houston
Jul 16, 2003·Nature·Pamela A WilliamsHarren Jhoti
Oct 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emily E ScottC David Stout
Oct 24, 2003·Protein Science : a Publication of the Protein Society·Timothy H Bayburt, Stephen G Sligar
Nov 25, 2003·Biochemical and Biophysical Research Communications·Dmitri R DavydovGaston Hui Bon Hoa
Mar 18, 2004·Journal of the American Chemical Society·I G DenisovS G Sligar
Jun 11, 2004·Annual Review of Biochemistry·Olena Pylypenko, Ilme Schlichting

❮ Previous
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Citations

Jul 16, 2008·Analytical and Bioanalytical Chemistry·Emre M Isin, F Peter Guengerich
Nov 8, 2011·Analytical and Bioanalytical Chemistry·Michael T MartyStephen G Sligar
Feb 8, 2014·Archives of Biochemistry and Biophysics·Benjamin J OrlandoMichael G Malkowski
Nov 8, 2007·Biochemistry·Aleksandra Z KijacChad M Rienstra
Oct 24, 2007·Journal of the American Chemical Society·Aditi DasStephen G Sligar
Jul 21, 2006·The Journal of Physical Chemistry. B·Ilia G DenisovStephen G Sligar
Feb 24, 2006·The Journal of Physical Chemistry. B·Amy Y ShihKlaus Schulten
Apr 8, 2011·The Journal of Biological Chemistry·Raku Shinkyo, F Peter Guengerich
Dec 24, 2011·The Journal of Biological Chemistry·Dmitri R DavydovJames R Halpert
Nov 24, 2007·The Journal of Biological Chemistry·Matthew R WhortonRoger K Sunahara
Apr 4, 2006·Physical Biology·Deyu LuKlaus Schulten
Oct 16, 2009·Journal of Virology·Palash BhattacharyaBellur S Prabhakar
Dec 3, 2010·Journal of Nanobiotechnology·Robert O Ryan
May 21, 2009·Biological Chemistry·Jonas Borch, Thomas Hamann
Nov 26, 2013·Advances in Colloid and Interface Science·Thomas Günther PomorskiMarité Cárdenas
Dec 2, 2008·Expert Opinion on Drug Metabolism & Toxicology·Dmitri R Davydov, James R Halpert
Sep 6, 2007·Drug Metabolism Reviews·Stephen G Sligar, Ilia G Denisov
Sep 6, 2007·Drug Metabolism Reviews·B K Muralidhara, James R Halpert
Jul 25, 2006·Expert Opinion on Drug Metabolism & Toxicology·William M Atkins
Jan 5, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Christopher J BenjaminDavid H Thompson
Mar 16, 2012·Thrombosis Research·James H MorrisseyChad M Rienstra
Jan 18, 2016·Journal of Inorganic Biochemistry·Ilia G DenisovJames R Kincaid
Aug 6, 2010·Biochimica Et Biophysica Acta·Ilia G Denisov, Stephen G Sligar
Jun 24, 2010·Current Opinion in Structural Biology·Thomas RaschleGerhard Wagner
Feb 5, 2010·Thrombosis Research·James H MorrisseyEmad Tajkhorshid
Jun 27, 2009·Pharmacology & Therapeutics·Ilia G DenisovStephen G Sligar
May 17, 2008·Biochemical and Biophysical Research Communications·Yelena V GrinkovaStephen G Sligar
Jul 28, 2009·Journal of Thrombosis and Haemostasis : JTH·J H MorrisseyE Tajkhorshid
Apr 5, 2013·Protein Science : a Publication of the Protein Society·Mahmoud L NasrAlexandros Makriyannis
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·J H MorrisseyC M Rienstra
Jan 18, 2005·Trends in Biochemical Sciences·Emily E Scott, James R Halpert
Oct 31, 2006·Journal of Structural Biology·Amy Y ShihKlaus Schulten
Oct 1, 2010·The Biochemical Journal·Yassar Farooq, Gordon C K Roberts
Apr 12, 2011·Biochimica Et Biophysica Acta·Dror E WarschawskiIsabelle Marcotte
Jul 6, 2010·Biochemical and Biophysical Research Communications·Yelena V GrinkovaStephen G Sligar

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