scholarly journals A substrate-binding-state mimic of H2O2-dependent cytochrome P450 produced by one-point mutagenesis and peroxygenation of non-native substrates

2016 ◽  
Vol 6 (15) ◽  
pp. 5806-5811 ◽  
Author(s):  
Osami Shoji ◽  
Takashi Fujishiro ◽  
Kousuke Nishio ◽  
Yukiko Kano ◽  
Hiroshi Kimoto ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Cytochrome P450s ◽  
Point Mutagenesis

H2O2-dependent cytochrome P450s that can catalyze monooxygenation of nonnative substrates were constructed by one-point mutagenesis.

Role of Cytochrome P450 in Tulip Bulb Probed by Substrate-Binding Studies

1992 ◽  
Vol 36 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Steven L. Kelly ◽  
Aysegul Topal ◽  
Ian Barnett ◽  
Diane E. Kelly ◽  
George A. F. Hendry
Keyword(s):  
Cytochrome P450 ◽  
Substrate Binding ◽  
Binding Studies ◽  
Tulip Bulb

Acetate anion-triggered peroxygenation of non-native substrates by wild-type cytochrome P450s

2015 ◽  
Vol 44 (34) ◽  
pp. 15316-15323 ◽  
Author(s):  
Hiroki Onoda ◽  
Osami Shoji ◽  
Yoshihito Watanabe
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450s ◽  
Acetate Anion ◽  
Wild Type ◽  
High Concentration

Wild-type cytochrome P450SPα and cytochrome P450BSβ can catalyze the oxidation of non-native substrates by performing the reaction at a high concentration of the acetate anion.

scholarly journals Aflatoxin B1 Conversion by Black Soldier Fly (Hermetia illucens) Larval Enzyme Extracts

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 532 ◽  
Author(s):  
Nathan Meijer ◽  
Geert Stoopen ◽  
H.J. van der Fels-Klerx ◽  
Joop J.A. van Loon ◽  
John Carney ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Aflatoxin B1 ◽  
Cytochrome P450s ◽  
Protein Source ◽  
Piperonyl Butoxide ◽  
Cytochrome P450 Enzymes ◽  
Black Soldier Fly ◽  
Hermetia Illucens ◽  
Food And Feed ◽  
Novel Protein

The larvae of the black soldier fly (Hermetia illucens L., BSFL) have received increased industrial interest as a novel protein source for food and feed. Previous research has found that insects, including BSFL, are capable of metabolically converting aflatoxin B1 (AFB1), but recovery of total AFB1 is less than 20% when accounting for its conversion to most known metabolites. The aim of this study was to examine the conversion of AFB1 by S9 extracts of BSFL reared on substrates with or without AFB1. Liver S9 of Aroclor-induced rats was used as a reference. To investigate whether cytochrome P450 enzymes are involved in the conversion of AFB1, the inhibitor piperonyl butoxide (PBO) was tested in a number of treatments. The results showed that approximately 60% of AFB1 was converted to aflatoxicol and aflatoxin P1. The remaining 40% of AFB1 was not converted. Cytochrome P450s were indeed responsible for metabolic conversion of AFB1 into AFP1, and a cytoplasmic reductase was most likely responsible for conversion of AFB1 into aflatoxicol.

scholarly journals A world of cytochrome P450s

2013 ◽  
Vol 368 (1612) ◽  
pp. 20120430 ◽  
Author(s):  
David R. Nelson
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450s ◽  
Rachel Carson ◽  
The Earth ◽  
The World

The world we live in is a biosphere influenced by all organisms who inhabit it. It is also an ecology of genes, with some having rather startling effects. The premise put forth in this issue is cytochrome P450 is a significant player in the world around us. Life and the Earth itself would be visibly different and diminished without cytochrome P450s. The contributions to this issue range from evolution on the billion year scale to the colour of roses, from Darwin to Rachel Carson; all as seen through the lens of cytochrome P450.

scholarly journals Multiple substrate-binding sites are retained in cytochrome P450 3A4 mutants with decreased cooperativity

Xenobiotica ◽  
2010 ◽  
Vol 41 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Harshica Fernando ◽  
Jessica A. O. Rumfeldt ◽  
Nadezhda Y. Davydova ◽  
James R. Halpert ◽  
Dmitri R. Davydov
Keyword(s):  
Cytochrome P450 ◽  
Binding Sites ◽  
Substrate Binding ◽  
Cytochrome P450 3A4 ◽  
Multiple Substrate ◽  
Substrate Binding Sites

scholarly journals Determining the IC50 Values for Vorozole and Letrozole, on a Series of Human Liver Cytochrome P450s, to Help Determine the Binding Site of Vorozole in the Liver

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Lendelle Raymond ◽  
Nikita Rayani ◽  
Grace Polson ◽  
Kylie Sikorski ◽  
Ailin Lian ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
High Throughput Screening ◽  
Human Liver ◽  
Potent Inhibitor ◽  
Cytochrome P450s ◽  
Third Generation ◽  
Weak Inhibitor ◽  
Liver Cytochrome ◽  
Ic50 Values ◽  
Screening Assays

Vorozole and letrozole are third-generation aromatase (cytochrome P450 19A1) inhibitors. [11C]-Vorozole can be used as a radiotracer for aromatase in living animals but when administered by IV, it collects in the liver. Pretreatment with letrozole does not affect the binding of vorozole in the liver. In search of finding the protein responsible for the accumulation of vorozole in the liver, fluorometric high-throughput screening assays were used to test the inhibitory capability of vorozole and letrozole on a series of liver cytochrome P450s (CYP1A1, CYP1A2, CYP2A6, and CYP3A4). It was determined that vorozole is a potent inhibitor of CYP1A1 (IC50 = 0.469 μM) and a moderate inhibitor of CYP2A6 and CYP3A4 (IC50 = 24.4 and 98.1 μM, resp.). Letrozole is only a moderate inhibitor of CYP1A1 and CYP2A6 (IC50 = 69.8 and 106 μM) and a very weak inhibitor of CYP3A4 (<10% inhibition at 1 mM). Since CYP3A4 makes up the majority of the CYP content found in the human liver, and vorozole inhibits it moderately well but letrozole does not, CYP3A4 is a good candidate for the protein that [11C]-vorozole is binding to in the liver.

scholarly journals Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics

1992 ◽  
Vol 281 (2) ◽  
pp. 359-368 ◽  
Author(s):  
L M Forrester ◽  
C J Henderson ◽  
M J Glancey ◽  
D J Back ◽  
B K Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Gene Families ◽  
Cytochrome P450s ◽  
Western Blots ◽  
Human Cytochrome ◽  
Wide Range ◽  
Powerful Approach ◽  
Highly Correlated ◽  
Gene Subfamily

Cytochrome P450s play a central role in the metabolism and disposition of an extremely wide range of drugs and chemical carcinogens. Individual differences in the expression of these enzymes may be an important determinant in susceptibility to adverse drug reactions, chemical toxins and mutagens. In this paper, we have measured the relative levels of expression of cytochrome P450 isoenzymes from eight gene families or subfamilies in a panel of twelve human liver samples in order to determine the individuality in their expression and whether any forms are co-regulated. Isoenzymes were identified in most cases on Western blots based on the mobility of authentic recombinant human cytochrome P450 standards. The levels of the following P450 proteins correlated with each other: CYP2A6, CYP2B6 and a protein from the CYP2C gene subfamily, CYP2E1 and a member of the CYP2A gene subfamily, CYP2C8, CYP3A3/A4 and total cytochrome P450 content. Also, the levels of two proteins in the CYP4A gene subfamily were highly correlated. These correlations are consistent with the relative regulation of members of these gene families in rats or mice. In addition, the level of expression of specific isoenzymes has also been compared with the rate of metabolism of a panel of drugs, carcinogens and model P450 substrates. These latter studies demonstrate and confirm that the correlations obtained in this manner represent a powerful approach towards the assignment of the metabolism of substrates by specific human P450 isoenzymes.

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