scholarly journals The central role of mosquito cytochrome P450 CYP6Zs in insecticide detoxification revealed by functional expression and structural modelling

2013 ◽  
Vol 455 (1) ◽  
pp. 75-85 ◽  
Author(s):  
Alexia Chandor-Proust ◽  
Jaclyn Bibby ◽  
Myriam Régent-Kloeckner ◽  
Jessica Roux ◽  
Emilie Guittard-Crilat ◽  
...  

The key role of mosquito cytochrome P450 monooxygenases from the CYP6Z subfamily in the resistance of mosquitoes to insecticides was revealed. By using functional expression and in silico modelling, the capacity of CYP6Zs to degrade insecticide metabolites produced by esterase-mediated hydrolysis was demonstrated.

2021 ◽  
Vol 67 (1) ◽  
Author(s):  
Ralf Nauen ◽  
Chris Bass ◽  
René Feyereisen ◽  
John Vontas

Insect cytochrome P450 monooxygenases (P450s) perform a variety of important physiological functions, but it is their role in the detoxification of xenobiotics, such as natural and synthetic insecticides, that is the topic of this review. Recent advances in insect genomics and postgenomic functional approaches have provided an unprecedented opportunity to understand the evolution of insect P450s and their role in insect toxicology. These approaches have also been harnessed to provide new insights into the genomic alterations that lead to insecticide resistance, the mechanisms by which P450s are regulated, and the functional determinants of P450-mediated insecticide resistance. In parallel, an emerging body of work on the role of P450s in defining the sensitivity of beneficial insects to insecticides has been developed. The knowledge gained from these studies has applications for the management of P450-mediated resistance in insect pests and can be leveraged to safeguard the health of important beneficial insects. Expected final online publication date for the Annual Review of Entomology, Volume 67 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2018 ◽  
Vol 1866 (1) ◽  
pp. 166-177 ◽  
Author(s):  
Retshedisitswe Godfrey Matowane ◽  
Lukasz Wieteska ◽  
Hans Denis Bamal ◽  
Ipeleng Kopano Rosinah Kgosiemang ◽  
Mari Van Wyk ◽  
...  

FEBS Journal ◽  
2010 ◽  
Vol 278 (2) ◽  
pp. 206-221 ◽  
Author(s):  
Inge N. A. Van Bogaert ◽  
Sara Groeneboer ◽  
Karen Saerens ◽  
Wim Soetaert

2021 ◽  
Vol 22 (15) ◽  
pp. 7811
Author(s):  
Olufunmilayo Olukemi Akapo ◽  
Joanna M. Macnar ◽  
Justyna D. Kryś ◽  
Puleng Rosinah Syed ◽  
Khajamohiddin Syed ◽  
...  

Cytochrome P450 monooxygenase CYP51 (sterol 14α-demethylase) is a well-known target of the azole drug fluconazole for treating cryptococcosis, a life-threatening fungal infection in immune-compromised patients in poor countries. Studies indicate that mutations in CYP51 confer fluconazole resistance on cryptococcal species. Despite the importance of CYP51 in these species, few studies on the structural analysis of CYP51 and its interactions with different azole drugs have been reported. We therefore performed in silico structural analysis of 11 CYP51s from cryptococcal species and other Tremellomycetes. Interactions of 11 CYP51s with nine ligands (three substrates and six azoles) performed by Rosetta docking using 10,000 combinations for each of the CYP51-ligand complex (11 CYP51s × 9 ligands = 99 complexes) and hierarchical agglomerative clustering were used for selecting the complexes. A web application for visualization of CYP51s’ interactions with ligands was developed (http://bioshell.pl/azoledocking/). The study results indicated that Tremellomycetes CYP51s have a high preference for itraconazole, corroborating the in vitro effectiveness of itraconazole compared to fluconazole. Amino acids interacting with different ligands were found to be conserved across CYP51s, indicating that the procedure employed in this study is accurate and can be automated for studying P450-ligand interactions to cater for the growing number of P450s.


Toxicology ◽  
1994 ◽  
Vol 93 (2-3) ◽  
pp. 165-173 ◽  
Author(s):  
Morio Fukuhara ◽  
Eric Antignac ◽  
Naomi Fukusen ◽  
Kazue Kato ◽  
Masanobu Kimura

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