TY - JOUR
T1 - Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin
AU - Ihara, Makoto
AU - Okajima, Toshihide
AU - Yamashita, Atsuko
AU - Oda, Takuma
AU - Hirata, Koichi
AU - Nishiwaki, Hisashi
AU - Morimoto, Takako
AU - Akamatsu, Miki
AU - Ashikawa, Yuji
AU - Kuroda, Shun'Ichi
AU - Mega, Ryosuke
AU - Kuramitsu, Seiki
AU - Sattelle, David B.
AU - Matsuda, Kazuhiko
PY - 2008/6/1
Y1 - 2008/6/1
N2 - Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR-neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH-π interactions in the Ls-AChBP-CTD complex than in the Ls-AChBP-IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs.
AB - Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR-neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH-π interactions in the Ls-AChBP-CTD complex than in the Ls-AChBP-IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs.
KW - Acetylcholine binding protein (Lymnaea stagnalis)
KW - Crystal structures
KW - Ion channels
KW - Neonicotinoids
KW - Nicotinic acetylcholine receptors
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U2 - 10.1007/s10158-008-0069-3
DO - 10.1007/s10158-008-0069-3
M3 - Article
C2 - 18338186
AN - SCOPUS:44449110466
VL - 8
SP - 71
EP - 81
JO - Invertebrate Neuroscience
JF - Invertebrate Neuroscience
SN - 1354-2516
IS - 2
ER -