Structural insights into the interaction between gabazine (SR-95531) and Laodelphax striatellus GABA receptors
γ-Aminobutyric acid receptors (GABARs) mediate fast inhibitory neurotransmission and are targets for insecticides. GABARs are composed of five subunits, the composition of which dictates the pharmacological characteristics of GABARs. Both competitive and noncompetitive GABAR antagonists can be used...
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| Veröffentlicht in: | Journal of Pesticide Science 2022/05/20, Vol.47(2), pp.78-85 |
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| creator | Fujie, Yuki Liu, Genyan Ozoe, Fumiyo Ozoe, Yoshihisa |
| description | γ-Aminobutyric acid receptors (GABARs) mediate fast inhibitory neurotransmission and are targets for insecticides. GABARs are composed of five subunits, the composition of which dictates the pharmacological characteristics of GABARs. Both competitive and noncompetitive GABAR antagonists can be used as insecticides. Gabazine is a potent competitive antagonist of mammalian α1β2γ2 GABARs; however, it is less potent against insect GABARs. To explore how gabazine interacts with GABARs, we examined whether the sensitivity of the small brown planthopper (Laodelphax striatellus) RDL GABAR (LsRDLR) to gabazine is increased when its amino acid residues are substituted with α1β2γ2 GABAR residues. In the results, two of the generated mutants showed enhanced gabazine sensitivity. Docking simulations of gabazine using LsRDLR homology models and an α1β2γ2 GABAR cryo-EM structure revealed that the accommodation of gabazine into the “aromatic box” in the orthosteric site lowered the binding energy. This information may help in designing GABAR-targeting insecticides with novel modes of action. |
| doi_str_mv | 10.1584/jpestics.D22-007 |
| format | Article |
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GABARs are composed of five subunits, the composition of which dictates the pharmacological characteristics of GABARs. Both competitive and noncompetitive GABAR antagonists can be used as insecticides. Gabazine is a potent competitive antagonist of mammalian α1β2γ2 GABARs; however, it is less potent against insect GABARs. To explore how gabazine interacts with GABARs, we examined whether the sensitivity of the small brown planthopper (Laodelphax striatellus) RDL GABAR (LsRDLR) to gabazine is increased when its amino acid residues are substituted with α1β2γ2 GABAR residues. In the results, two of the generated mutants showed enhanced gabazine sensitivity. Docking simulations of gabazine using LsRDLR homology models and an α1β2γ2 GABAR cryo-EM structure revealed that the accommodation of gabazine into the “aromatic box” in the orthosteric site lowered the binding energy. This information may help in designing GABAR-targeting insecticides with novel modes of action.</description><identifier>ISSN: 1348-589X</identifier><identifier>EISSN: 1349-0923</identifier><identifier>DOI: 10.1584/jpestics.D22-007</identifier><identifier>PMID: 35800394</identifier><language>eng</language><publisher>Tokyo: Pesticide Science Society of Japan</publisher><subject>Amino acids ; Antagonists ; Chemical compounds ; competitive antagonist ; GABA receptor ; gabazine ; Homology ; insecticide ; Insecticides ; Insects ; Laodelphax striatellus ; Neurotransmission ; Pharmaceuticals ; Receptors ; Regular ; Residues ; Sensitivity enhancement ; small brown planthopper ; γ-Aminobutyric acid ; γ-Aminobutyric acid receptors</subject><ispartof>Journal of Pesticide Science, 2022/05/20, Vol.47(2), pp.78-85</ispartof><rights>Pesticide Science Society of Japan 2022. 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Pestic. Sci.</addtitle><description>γ-Aminobutyric acid receptors (GABARs) mediate fast inhibitory neurotransmission and are targets for insecticides. GABARs are composed of five subunits, the composition of which dictates the pharmacological characteristics of GABARs. Both competitive and noncompetitive GABAR antagonists can be used as insecticides. Gabazine is a potent competitive antagonist of mammalian α1β2γ2 GABARs; however, it is less potent against insect GABARs. To explore how gabazine interacts with GABARs, we examined whether the sensitivity of the small brown planthopper (Laodelphax striatellus) RDL GABAR (LsRDLR) to gabazine is increased when its amino acid residues are substituted with α1β2γ2 GABAR residues. In the results, two of the generated mutants showed enhanced gabazine sensitivity. Docking simulations of gabazine using LsRDLR homology models and an α1β2γ2 GABAR cryo-EM structure revealed that the accommodation of gabazine into the “aromatic box” in the orthosteric site lowered the binding energy. This information may help in designing GABAR-targeting insecticides with novel modes of action.</description><subject>Amino acids</subject><subject>Antagonists</subject><subject>Chemical compounds</subject><subject>competitive antagonist</subject><subject>GABA receptor</subject><subject>gabazine</subject><subject>Homology</subject><subject>insecticide</subject><subject>Insecticides</subject><subject>Insects</subject><subject>Laodelphax striatellus</subject><subject>Neurotransmission</subject><subject>Pharmaceuticals</subject><subject>Receptors</subject><subject>Regular</subject><subject>Residues</subject><subject>Sensitivity enhancement</subject><subject>small brown planthopper</subject><subject>γ-Aminobutyric acid</subject><subject>γ-Aminobutyric acid receptors</subject><issn>1348-589X</issn><issn>1349-0923</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kc1rFDEYxgdRbKm9exzwUg_T5nOSXIS12lpYEKyCt5DJvLuTZTYZk0z9-OvNuuuKHrwkL-T3PLxPnqp6jtEl5pJdbSZI2dl0-YaQBiHxqDrFlKkGKUIf_5plw6X6fFKdp7RBCGFBhVLt0-qEcokQVey08vc5zjbP0Yy188mth5zKkEOdB9gNEI3NLvi6g_wVwNdr05kfzkN9cf-hUZxT_LI2vq-XJvQwToP5VqccnckwjnOqbxevF3UEC1MOMT2rnqzMmOD8cJ9Vn27efrx-1yzf395dL5aN5RjnhnQcS8RXjCuLBOYIEaKwQVipXiDbd7wzCinaEtJ2pqdsBSAxdBKrjveW0LPq1d53mrst9BZ8Lgn1FN3WxO86GKf_fvFu0OvwoBWWjDBZDC4OBjF8mctH661LtkQyHsKcNGmlEATTFhX0xT_oJszRl3iaCM5KVZKS_1KtIFTQlqlCoT1lY0gpwuq4MkZ617r-3bourevSepHc7CWblM0ajgITCzbCHwETmuyOg_AI2MFEDZ7-BHkzuaE</recordid><startdate>20220520</startdate><enddate>20220520</enddate><creator>Fujie, Yuki</creator><creator>Liu, Genyan</creator><creator>Ozoe, Fumiyo</creator><creator>Ozoe, Yoshihisa</creator><general>Pesticide Science Society of Japan</general><general>Japan Science and Technology Agency</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>SOI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220520</creationdate><title>Structural insights into the interaction between gabazine (SR-95531) and Laodelphax striatellus GABA receptors</title><author>Fujie, Yuki ; Liu, Genyan ; Ozoe, Fumiyo ; Ozoe, Yoshihisa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-2b51805f459c0715002291a0199d70cdb5ba90936226bad34fee81eb819b5dc23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Amino acids</topic><topic>Antagonists</topic><topic>Chemical compounds</topic><topic>competitive antagonist</topic><topic>GABA receptor</topic><topic>gabazine</topic><topic>Homology</topic><topic>insecticide</topic><topic>Insecticides</topic><topic>Insects</topic><topic>Laodelphax striatellus</topic><topic>Neurotransmission</topic><topic>Pharmaceuticals</topic><topic>Receptors</topic><topic>Regular</topic><topic>Residues</topic><topic>Sensitivity enhancement</topic><topic>small brown planthopper</topic><topic>γ-Aminobutyric acid</topic><topic>γ-Aminobutyric acid receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujie, Yuki</creatorcontrib><creatorcontrib>Liu, Genyan</creatorcontrib><creatorcontrib>Ozoe, Fumiyo</creatorcontrib><creatorcontrib>Ozoe, Yoshihisa</creatorcontrib><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of Pesticide Science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujie, Yuki</au><au>Liu, Genyan</au><au>Ozoe, Fumiyo</au><au>Ozoe, Yoshihisa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural insights into the interaction between gabazine (SR-95531) and Laodelphax striatellus GABA receptors</atitle><jtitle>Journal of Pesticide Science</jtitle><addtitle>J. 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In the results, two of the generated mutants showed enhanced gabazine sensitivity. Docking simulations of gabazine using LsRDLR homology models and an α1β2γ2 GABAR cryo-EM structure revealed that the accommodation of gabazine into the “aromatic box” in the orthosteric site lowered the binding energy. This information may help in designing GABAR-targeting insecticides with novel modes of action.</abstract><cop>Tokyo</cop><pub>Pesticide Science Society of Japan</pub><pmid>35800394</pmid><doi>10.1584/jpestics.D22-007</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese; PubMed Central |
| subjects | Amino acids Antagonists Chemical compounds competitive antagonist GABA receptor gabazine Homology insecticide Insecticides Insects Laodelphax striatellus Neurotransmission Pharmaceuticals Receptors Regular Residues Sensitivity enhancement small brown planthopper γ-Aminobutyric acid γ-Aminobutyric acid receptors |
| title | Structural insights into the interaction between gabazine (SR-95531) and Laodelphax striatellus GABA receptors |
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