» Articles » PMID: 29383143

Functional Characterization of a Unique Cytochrome P450 in

Overview
Journal Oncotarget
Specialty Oncology
Date 2018 Feb 1
PMID 29383143
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

The basic metabolic cytochrome P450 (CYP) proteins are essential for the biotransformation of sterols and xenobiotics. By contrast, the genome contains only one CYP gene, and the role of this enzyme in the physiology and biochemistry of apicomplexan parasites is unknown. Because it is a potential resistance gene, identifying the functionality of P450 in is particularly important. Knocking out had no significant effect on survival, but mice infected with parasites overexpressing exhibited significantly enhanced pathogenicity. Enzyme activity analyses demonstrated that this protein has mammalian CYP2B and CYP3A enzymatic activity. In addition, lacking the P450 gene exhibited reduced resistance to quinine, mefloquine and clarithromycin compared with parasites overexpressing Tg-P450. These results suggest that P450 functions in metabolism and detoxification is involved in vitally important processes in parasitic organisms, making this enzyme a potential drug target.

Citing Articles

Early Transcriptional Response to Monensin in Sensitive and Resistant Strains of .

Zhang H, Zhang L, Si H, Liu X, Suo X, Hu D Front Microbiol. 2022; 13:934153.

PMID: 35859739 PMC: 9289555. DOI: 10.3389/fmicb.2022.934153.


Cytochrome P450 monooxygenase of Acanthamoeba castellanii participates in resistance to polyhexamethylene biguanide treatment.

Huang J, Ko P, Huang C, Wen P, Chen C, Shih M Parasite. 2021; 28:77.

PMID: 34762043 PMC: 8582484. DOI: 10.1051/parasite/2021074.


Derivatives of the Antimalarial Drug Mefloquine Are Broad-Spectrum Antifungal Molecules with Activity against Drug-Resistant Clinical Isolates.

Montoya M, Beattie S, Alden K, Krysan D Antimicrob Agents Chemother. 2020; 64(3).

PMID: 31907188 PMC: 7038245. DOI: 10.1128/AAC.02331-19.


Drug Screening for Discovery of Broad-spectrum Agents for Soil-transmitted Nematodes.

Elfawal M, Savinov S, Aroian R Sci Rep. 2019; 9(1):12347.

PMID: 31451730 PMC: 6710243. DOI: 10.1038/s41598-019-48720-1.

References
1.
Na-Bangchang K, Bray P, Ward S . Study on the biochemical basis of mefloquine resistant Plasmodium falciparum. Exp Parasitol. 2007; 117(2):141-8. DOI: 10.1016/j.exppara.2007.04.002. View

2.
Cvilink V, Lamka J, Skalova L . Xenobiotic metabolizing enzymes and metabolism of anthelminthics in helminths. Drug Metab Rev. 2009; 41(1):8-26. DOI: 10.1080/03602530802602880. View

3.
Hlavica P . On the function of cytochrome b5 in the cytochrome P-450-dependent oxygenase system. Arch Biochem Biophys. 1984; 228(2):600-8. DOI: 10.1016/0003-9861(84)90028-6. View

4.
Turman C, Hatley J, Ryder D, Ravindranath V, Strobel H . Alternative splicing within the human cytochrome P450 superfamily with an emphasis on the brain: The convolution continues. Expert Opin Drug Metab Toxicol. 2006; 2(3):399-418. DOI: 10.1517/17425255.2.3.399. View

5.
Burke M, Thompson S, Weaver R, Wolf C, Mayer R . Cytochrome P450 specificities of alkoxyresorufin O-dealkylation in human and rat liver. Biochem Pharmacol. 1994; 48(5):923-36. DOI: 10.1016/0006-2952(94)90363-8. View