Structural model for gamma-aminobutyric acid receptor noncompetitive antagonist binding: widely diverse structures fit the same site

Proceedings of the National Academy of Sciences of the United States of America
Ligong ChenJohn E Casida

Abstract

Several major insecticides, including alpha-endosulfan, lindane, and fipronil, and the botanical picrotoxinin are noncompetitive antagonists (NCAs) for the GABA receptor. We showed earlier that human beta(3) homopentameric GABA(A) receptor recognizes all of the important GABAergic insecticides and reproduces the high insecticide sensitivity and structure-activity relationships of the native insect receptor. Despite large structural diversity, the NCAs are proposed to fit a single binding site in the chloride channel lumen lined by five transmembrane 2 segments. This hypothesis is examined with the beta(3) homopentamer by mutagenesis, pore structure studies, NCA binding, and molecular modeling. The 15 amino acids in the cytoplasmic half of the pore were mutated to cysteine, serine, or other residue for 22 mutants overall. Localization of A-1'C, A2'C, T6'C, and L9'C (index numbers for the transmembrane 2 region) in the channel lumen was established by disulfide cross-linking. Binding of two NCA radioligands [(3)H]1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane and [(3)H] 3,3-bis-trifluoromethyl-bicyclo[2,2,1]heptane-2,2-dicarbonitrile was dramatically reduced with 8 of the 15 mutated positions, focusing attention ...Continue Reading

References

Jan 1, 1983·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·F Matsumura, S M Ghiasuddin
Jan 1, 1993·Archives of Insect Biochemistry and Physiology·J E Casida
Feb 1, 1993·Journal of Computer-aided Molecular Design·J A CalderJ E Casida
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·D ZhangS A Lipton
Jan 28, 1998·Annual Review of Entomology·J E Casida, G B Quistad
Feb 17, 1998·The European Journal of Neuroscience·J R WooltortonT G Smart
Apr 13, 2000·Annual Review of Entomology·R H Ffrench-ConstantG Stilwell
Jul 6, 2000·Journal of Neuroscience Research·L ElsterR W Olsen
Aug 31, 2000·Annual Review of Biochemistry·J L Popot, D M Engelman
Apr 21, 2001·Toxicology and Applied Pharmacology·G S RatraJ E Casida
Aug 8, 2001·Toxicology Letters·G S Ratra, J E Casida
Jul 20, 2002·Progress in Neurobiology·Esa R KorpiHartmut Lüddens
Jun 27, 2003·Nature·Atsuo MiyazawaNigel Unwin
Jan 13, 2004·The Journal of Biological Chemistry·Eric N GorenMyles H Akabas
Mar 8, 2005·Biophysical Journal·Megan O'MaraShin-Ho Chung

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Citations

Aug 12, 2010·Journal of Agricultural and Food Chemistry·John E Casida
Sep 14, 2013·Chemical Research in Toxicology·Timothy S CarpenterFelice C Lightstone
Jan 19, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Andrew J ThompsonSarah C R Lummis
Sep 11, 2010·Journal of Biomedical Science·William J L'AmoreauxAbdeslem El Idrissi
Apr 12, 2006·Proceedings of the National Academy of Sciences of the United States of America·Richard W Olsen
Jan 16, 2013·Annual Review of Entomology·John E Casida, Kathleen A Durkin
Jun 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Chunqing ZhaoJohn E Casida
Oct 12, 2014·Molecular and Cellular Neurosciences·Alexey V RossokhinVladimir G Skrebitsky
Sep 7, 2014·Insect Biochemistry and Molecular Biology·Emily J RemnantPhilip Batterham
May 1, 2008·The International Journal of Neuroscience·Richard J Law, Felice C Lightstone
Jan 3, 2016·Regulatory Toxicology and Pharmacology : RTP·Zachary A CollierEdward J Perkins
Apr 30, 2016·ACS Chemical Biology·Peter Man-Un UngAvner Schlessinger
Nov 30, 2010·Toxicology and Applied Pharmacology·Ligong ChenJohn E Casida
May 20, 2015·Pesticide Biochemistry and Physiology·Toshifumi NakaoKangetsu Hirase
Jan 3, 2012·Biophysical Journal·Mona AlqazzazSarah C R Lummis
Jun 6, 2015·Pesticide Biochemistry and Physiology·Toshifumi Nakao, Shinichi Banba
Jan 27, 2015·Pesticide Biochemistry and Physiology·Feng JiangZewen Liu
Jun 6, 2015·Pesticide Biochemistry and Physiology·John E Casida, Kathleen A Durkin
Aug 24, 2007·Journal of Neurochemistry·Zhe YangJoseph W Lynch
Jun 29, 2010·Journal of Applied Toxicology : JAT·Iván Restrepo-AnguloJavier Camacho
Oct 20, 2006·The Journal of Biological Chemistry·Ligong ChenJohn E Casida
Apr 5, 2007·The Journal of Biological Chemistry·Dian-Shi WangPascal Legendre
Nov 1, 2011·British Journal of Pharmacology·Robiul Islam, Joseph W Lynch

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