Tags

Type your tag names separated by a space and hit enter

Structural model and functional characterization of the Bemisia tabaci CYP6CM1vQ, a cytochrome P450 associated with high levels of imidacloprid resistance.
Insect Biochem Mol Biol. 2009 Oct; 39(10):697-706.IB

Abstract

The neonicotinoid imidacloprid is one of the most important insecticides worldwide. It is used extensively against the whitefly Bemisia tabaci (Hemiptera: Aleyrodidae), an insect pest of eminent importance globally, which was also the first pest to develop high levels of resistance against imidacloprid and other neonicotinoids in the field. Recent reports indicated that in both the B and Q biotypes of B. tabaci, the resistant phenotype is associated with over-expression of the cytochrome P450 gene CYP6CM1. In this study, molecular docking and dynamic simulations were used to analyze interactions of imidacloprid with the biotype Q variant of the CYP6CM1 enzyme (CYP6CM1vQ). The binding mode with the lowest energy in the enzyme active site, the key amino acids involved (i.e. Phe-130 and Phe-226), and the putative hydroxylation site (lowest distance to carbon 5 of the imidazolidine ring system of imidacloprid) were predicted. Heterologous expression of the CYP6CM1vQ confirmed the accuracy of our predictions and demonstrated that the enzyme catalyses the hydroxylation of imidacloprid to its less toxic 5-hydroxy form (K(cat) = 3.2 pmol/min/pmol P450, K(m) = 36 microM). The data identify CYP6CM1vQ as a principle target for inhibitor design, aimed at inactivating insecticide-metabolizing P450s in natural insect pest populations.

Links

Publisher Full Text

Authors+Show Affiliations

Karunker I
Department of Entomology, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot, Israel.
Morou E
No affiliation info available
Nikou D
No affiliation info available
Nauen R
No affiliation info available
Sertchook R
No affiliation info available
Stevenson BJ
No affiliation info available
Paine MJ
No affiliation info available
Morin S
No affiliation info available
Vontas J
No affiliation info available

MeSH

Amino Acid SequenceAnimalsBinding SitesCytochrome P-450 Enzyme SystemHemipteraImidazolesInsect ProteinsInsecticide ResistanceInsecticidesModels, MolecularMolecular Sequence DataNeonicotinoidsNitro CompoundsSequence Alignment

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19716416

Citation

Karunker, Iris, et al. "Structural Model and Functional Characterization of the Bemisia Tabaci CYP6CM1vQ, a Cytochrome P450 Associated With High Levels of Imidacloprid Resistance." Insect Biochemistry and Molecular Biology, vol. 39, no. 10, 2009, pp. 697-706.
Karunker I, Morou E, Nikou D, et al. Structural model and functional characterization of the Bemisia tabaci CYP6CM1vQ, a cytochrome P450 associated with high levels of imidacloprid resistance. Insect Biochem Mol Biol. 2009;39(10):697-706.
Karunker, I., Morou, E., Nikou, D., Nauen, R., Sertchook, R., Stevenson, B. J., Paine, M. J., Morin, S., & Vontas, J. (2009). Structural model and functional characterization of the Bemisia tabaci CYP6CM1vQ, a cytochrome P450 associated with high levels of imidacloprid resistance. Insect Biochemistry and Molecular Biology, 39(10), 697-706. https://doi.org/10.1016/j.ibmb.2009.08.006
Karunker I, et al. Structural Model and Functional Characterization of the Bemisia Tabaci CYP6CM1vQ, a Cytochrome P450 Associated With High Levels of Imidacloprid Resistance. Insect Biochem Mol Biol. 2009;39(10):697-706. PubMed PMID: 19716416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural model and functional characterization of the Bemisia tabaci CYP6CM1vQ, a cytochrome P450 associated with high levels of imidacloprid resistance. AU - Karunker,Iris, AU - Morou,Evangelia, AU - Nikou,Dimitra, AU - Nauen,Ralf, AU - Sertchook,Rotem, AU - Stevenson,Bradley J, AU - Paine,Mark J I, AU - Morin,Shai, AU - Vontas,John, Y1 - 2009/08/27/ PY - 2009/07/14/received PY - 2009/08/12/revised PY - 2009/08/13/accepted PY - 2009/9/1/entrez PY - 2009/9/1/pubmed PY - 2009/12/16/medline SP - 697 EP - 706 JF - Insect biochemistry and molecular biology JO - Insect Biochem Mol Biol VL - 39 IS - 10 N2 - The neonicotinoid imidacloprid is one of the most important insecticides worldwide. It is used extensively against the whitefly Bemisia tabaci (Hemiptera: Aleyrodidae), an insect pest of eminent importance globally, which was also the first pest to develop high levels of resistance against imidacloprid and other neonicotinoids in the field. Recent reports indicated that in both the B and Q biotypes of B. tabaci, the resistant phenotype is associated with over-expression of the cytochrome P450 gene CYP6CM1. In this study, molecular docking and dynamic simulations were used to analyze interactions of imidacloprid with the biotype Q variant of the CYP6CM1 enzyme (CYP6CM1vQ). The binding mode with the lowest energy in the enzyme active site, the key amino acids involved (i.e. Phe-130 and Phe-226), and the putative hydroxylation site (lowest distance to carbon 5 of the imidazolidine ring system of imidacloprid) were predicted. Heterologous expression of the CYP6CM1vQ confirmed the accuracy of our predictions and demonstrated that the enzyme catalyses the hydroxylation of imidacloprid to its less toxic 5-hydroxy form (K(cat) = 3.2 pmol/min/pmol P450, K(m) = 36 microM). The data identify CYP6CM1vQ as a principle target for inhibitor design, aimed at inactivating insecticide-metabolizing P450s in natural insect pest populations. SN - 1879-0240 UR - https://www.unboundmedicine.com/medline/citation/19716416/Structural_model_and_functional_characterization_of_the_Bemisia_tabaci_CYP6CM1vQ_a_cytochrome_P450_associated_with_high_levels_of_imidacloprid_resistance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0965-1748(09)00125-8 DB - PRIME DP - Unbound Medicine ER -