The catalytic function of cytochrome P450 is entwined with its membrane-bound nature

F1000Research
Carlo BarnabaAyyalusamy Ramamoorthy

Abstract

Cytochrome P450, a family of monooxygenase enzymes, is organized as a catalytic metabolon, which requires enzymatic partners as well as environmental factors that tune its complex dynamic. P450 and its reducing counterparts-cytochrome P450-reductase and cytochrome b 5 -are membrane-bound proteins located in the cytosolic side of the endoplasmic reticulum. They are believed to dynamically associate to form functional complexes. Increasing experimental evidence signifies the role(s) played by both protein-protein and protein-lipid interactions in P450 catalytic function and efficiency. However, the biophysical challenges posed by their membrane-bound nature have severely limited high-resolution understanding of the molecular interfaces of these interactions. In this article, we provide an overview of the current knowledge on cytochrome P450, highlighting the environmental factors that are entwined with its metabolic function. Recent advances in structural biophysics are also discussed, setting up the bases for a new paradigm in the study of this important class of membrane-bound enzymes.

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Citations

May 22, 2018·Chemical Communications : Chem Comm·Katherine A GentryAyyalusamy Ramamoorthy
Nov 17, 2017·Chemical Communications : Chem Comm·Thirupathi RavulaAyyalusamy Ramamoorthy
Jun 1, 2018·International Journal of Molecular Sciences·Philippe UrbanGilles Truan
Jun 5, 2018·Chemical Communications : Chem Comm·Carlo BarnabaAyyalusamy Ramamoorthy
Aug 11, 2018·Chemical Communications : Chem Comm·Thirupathi RavulaAyyalusamy Ramamoorthy
Jul 12, 2018·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Carlo Barnaba, Ayyalusamy Ramamoorthy
Feb 1, 2018·Angewandte Chemie·Carlo BarnabaAyyalusamy Ramamoorthy
Sep 17, 2020·International Journal of Molecular Sciences·Francisco EstevesMichel Kranendonk
Mar 30, 2018·Current Opinion in Structural Biology·Charles R Sanders, James M Hutchison
Jul 23, 2020·International Journal of Biological Macromolecules·Chao ZhangGianfranco Gilardi
Mar 20, 2021·ChemMedChem·Angelo SpinelloAlessandra Magistrato
Jul 2, 2021·Applied Microbiology and Biotechnology·Xuan ZhouLong Liu
Dec 7, 2017·Journal of the American Chemical Society·Sigrun RumpelWolfgang Lubitz
Sep 19, 2017·Langmuir : the ACS Journal of Surfaces and Colloids·Thirupathi RavulaAyyalusamy Ramamoorthy
Nov 9, 2021·ACS Synthetic Biology·Meghan E DaviesVincent J J Martin

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Methods Mentioned

BETA
nuclear magnetic resonance
NMR
x-ray crystallography
protein folding
x-ray crystallographic

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