Cytochromes P450 in Nanodiscs

被引:71
作者
Denisov, Ilia G. [1 ]
Sligar, Stephen G. [1 ]
机构
[1] Univ Illinois, Sch Mol & Cellular Biol, Dept Biochem, Urbana, IL 61801 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2011年 / 1814卷 / 01期
关键词
Cytochrome P450; Monooxygenase; Membrane protein; Nanodisc; Reaction intermediates; PHOSPHOLIPID-BILAYER NANODISCS; NANOSCALE LIPID-BILAYERS; MOLECULE HEIGHT MEASUREMENTS; DRUG-DRUG INTERACTIONS; RESONANCE RAMAN; MEMBRANE-PROTEINS; SPIN EQUILIBRIUM; LIGAND-BINDING; NADPH-CYTOCHROME-P-450; REDUCTASE; MICROSOMAL CYTOCHROME-P-450;
D O I
10.1016/j.bbapap.2010.05.017
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nanodiscs have proven to be a versatile tool for the study all types of membrane proteins, including receptors, transporters, enzymes and viral antigens. The self-assembled Nanodisc system provides a robust and common means for rendering these targets soluble in aqueous media while providing a native like bilayer environment that maintains functional activity. This system has thus provided a means for studying the extensive collection of membrane bound cytochromes P450 with the same biochemical and biophysical tools that have been previously limited to use with the soluble P450s. These include a plethora of spectroscopic, kinetic and surface based methods. Significant improvements in homogeneity and stability of these preparations open new possibilities for detailed analysis of equilibrium and steady-state kinetic characteristics of catalytic mechanisms of human cytochromes P450 involved in xenobiotic metabolism and in steroid biosynthesis. The experimental methods developed for physico-chemical and functional studies of membrane cytochromes P450 incorporated in Nanodiscs allow for more detailed understanding of the scientific questions along the lines pioneered by Professor Klaus Ruckpaul and his array of colleagues and collaborators. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:223 / 229
页数:7
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