Molecular action of larvicidal flavonoids on ecdysteroidogenic glutathione S-transferase Noppera-bo in Aedes aegypti

Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein,...

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Published inBMC biology Vol. 20; no. 1; pp. 43 - 20
Main Authors Inaba, Kazue, Ebihara, Kana, Senda, Miki, Yoshino, Ryunosuke, Sakuma, Chisako, Koiwai, Kotaro, Takaya, Daisuke, Watanabe, Chiduru, Watanabe, Akira, Kawashima, Yusuke, Fukuzawa, Kaori, Imamura, Riyo, Kojima, Hirotatsu, Okabe, Takayoshi, Uemura, Nozomi, Kasai, Shinji, Kanuka, Hirotaka, Nishimura, Takashi, Watanabe, Kodai, Inoue, Hideshi, Fujikawa, Yuuta, Honma, Teruki, Hirokawa, Takatsugu, Senda, Toshiya, Niwa, Ryusuke
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 17.02.2022
BioMed Central
BMC
Subjects
Aedes
Aedes aegypti
Analysis
Animals
Binding sites
Biosynthesis
Chemical compounds
Control
Crystal structure
Crystals
Daidzein
Dengue fever
Developmental stages
Ecdysone
Ecdysteroid
Enzymes
Flavonoid
Flavonoids
Glutathione
Glutathione S-transferase
Glutathione transferase
Glutathione Transferase - metabolism
Health aspects
Humans
Hydrogen bonds
Infectious diseases
Inhibitors
Insect control
Insect growth regulator
Insecticides
Insects
Larva
Larval development
Larvicides
Methods
Mode of action
Molecular dynamics
Mosquito Control
Mosquitoes
Mutation
Phenolic compounds
Phenols
Protein structure
Proteins
Reagents
Structure
Tropical diseases
Vector-borne diseases
Viruses
Yellow fever
Japan
Ecdysteroid
Noppera-bo
Insecticide
Mosquito
Aedes aegypti
Ecdysone
Insect growth regulator
Glutathione S-transferase
Flavonoid
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Abstract Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated. Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4',6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein. Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.
AbstractList Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated. Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4',6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein. Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.
Abstract Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated. Results Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4′,6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein. Conclusion Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.
Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated. Results Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4',6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein. Conclusion Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels. Keywords: Aedes aegypti, Ecdysone, Ecdysteroid, Flavonoid, Glutathione S-transferase, Insect growth regulator, Insecticide, Mosquito, Noppera-bo
Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated. Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4',6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein. Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.
Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated.BACKGROUNDMosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated.Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4',6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein.RESULTSHere, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4',6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein.Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.CONCLUSIONOur study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.
Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of selective and safe reagents for mosquito control. Flavonoids, a group of chemical substances with variable phenolic structures, such as daidzein, have been suggested as potential mosquito larvicides with less risk to the environment. However, the mode of mosquito larvicidal action of flavonoids has not been elucidated. Results Here, we report that several flavonoids, including daidzein, inhibit the activity of glutathione S-transferase Noppera-bo (Nobo), an enzyme used for the biosynthesis of the insect steroid hormone ecdysone, in the yellow fever mosquito Aedes aegypti. The crystal structure of the Nobo protein of Ae. aegypti (AeNobo) complexed with the flavonoids and its molecular dynamics simulation revealed that Glu113 forms a hydrogen bond with the flavonoid inhibitors. Consistent with this observation, substitution of Glu113 with Ala drastically reduced the inhibitory activity of the flavonoids against AeNobo. Among the identified flavonoid-type inhibitors, desmethylglycitein (4′,6,7-trihydroxyisoflavone) exhibited the highest inhibitory activity in vitro. Moreover, the inhibitory activities of the flavonoids correlated with the larvicidal activity, as desmethylglycitein suppressed Ae. aegypti larval development more efficiently than daidzein. Conclusion Our study demonstrates the mode of action of flavonoids on the Ae. aegypti Nobo protein at the atomic, enzymatic, and organismal levels.
ArticleNumber 43
Audience Academic
Author Inaba, Kazue
Niwa, Ryusuke
Kojima, Hirotatsu
Watanabe, Chiduru
Senda, Toshiya
Watanabe, Kodai
Fukuzawa, Kaori
Honma, Teruki
Koiwai, Kotaro
Inoue, Hideshi
Okabe, Takayoshi
Nishimura, Takashi
Imamura, Riyo
Sakuma, Chisako
Uemura, Nozomi
Kanuka, Hirotaka
Kawashima, Yusuke
Kasai, Shinji
Ebihara, Kana
Senda, Miki
Yoshino, Ryunosuke
Watanabe, Akira
Fujikawa, Yuuta
Takaya, Daisuke
Hirokawa, Takatsugu
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/35172816$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Ecdysteroid
Noppera-bo
Insecticide
Mosquito
Aedes aegypti
Ecdysone
Insect growth regulator
Glutathione S-transferase
Flavonoid
Language English
License 2022. The Author(s).
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Snippet Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the development of...
Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the...
Abstract Background Mosquito control is a crucial global issue for protecting the human community from mosquito-borne diseases. There is an urgent need for the...
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StartPage 43
SubjectTerms Aedes
Aedes aegypti
Analysis
Animals
Binding sites
Biosynthesis
Chemical compounds
Control
Crystal structure
Crystals
Daidzein
Dengue fever
Developmental stages
Ecdysone
Ecdysteroid
Enzymes
Flavonoid
Flavonoids
Glutathione
Glutathione S-transferase
Glutathione transferase
Glutathione Transferase - metabolism
Health aspects
Humans
Hydrogen bonds
Infectious diseases
Inhibitors
Insect control
Insect growth regulator
Insecticides
Insects
Larva
Larval development
Larvicides
Methods
Mode of action
Molecular dynamics
Mosquito Control
Mosquitoes
Mutation
Phenolic compounds
Phenols
Protein structure
Proteins
Reagents
Structure
Tropical diseases
Vector-borne diseases
Viruses
Yellow fever
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Title Molecular action of larvicidal flavonoids on ecdysteroidogenic glutathione S-transferase Noppera-bo in Aedes aegypti
URI https://www.ncbi.nlm.nih.gov/pubmed/35172816
https://www.proquest.com/docview/2630432026
https://www.proquest.com/docview/2629860760
https://pubmed.ncbi.nlm.nih.gov/PMC8851771
https://doaj.org/article/b49433e4465946a08dd1ecf88c040e05
Volume 20
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