Molecular characterization of an acetylcholinesterase from the hemichordate Saccoglossus kowalevskii

Pezzementi, Leo; Geiss, Cybil; King, W. T.; Lenfant, Nicolas; Chatonnet, Arnaud

doi:10.1016/j.cbpb.2014.11.005

Cited by 3 publications

(2 citation statements)

References 57 publications

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“…Based on parallels in catalytic properties with these other α,β−hydrolase-fold enzymes, we would predict the following sequence characteristics for DjChE: (a) classic catalytic triad resembling Ser200, Glu327 and His440 in the Torpedo californica sequence (Schumacher et al 1986) and three disulfide bonded loops, (b) an acyl pocket corresponding to Phe295 and 297 that contains only a single aromatic residue, (c) a choline binding site dominated by Trp84 which serves a major role in the binding of quaternary inhibitors, (d) the absence or severe disruption of a peripheral anionic site defined by Trp286, Tyr72, and Tyr124, (e) a reduced number of aromatic side chains in the active center gorge compared with AChE, and (f) the absence of a clear distinction between AChE and BChE binding, where ethopropazine is selective for BChE. Future sequence identification and functional characterization of DjChE allow for a direct comparison with the published sequences from Schistosomes (Bentley et al 2003), hagfish (Sanders et al 1996), hemichordates (Pezzementi et al 2015), and nematodes (Combes et al 2001) to verify these proposed sequence features.…”

Section: Discussionmentioning

confidence: 99%

Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation

et al. 2016

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The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D. japonica cholinesterase (DjChE) activity departs from conventional AChE and BChE classifications. Inhibition by classic protonable amine and quaternary reversible inhibitors (ethopropazine, donepezil, tacrine, edrophonium, BW284c51, propidium) shows that DjChE is far less sensitive to these inhibitors than human AChE, suggesting discrete differences in active center and peripheral site recognition and structures. Additionally, we find that different OPs (chlorpyrifos oxon, paraoxon, dichlorvos, diazinon oxon, malaoxon) and carbamylating agents (carbaryl, neostigmine, physostigmine, pyridostigmine) differentially inhibit DjChE activity in vitro. DjChE was most sensitive to diazinon oxon and neostigmine and least sensitive to malaoxon and carbaryl. Diazinon oxon-inhibited DjChE could be reactivated by the quaternary oxime, pralidoxime (2-PAM), and the zwitterionic oxime, RS194B, with RS194B being significantly more potent. Sodium fluoride (NaF) reactivates OP-DjChE faster than 2-PAM. As one of the most ancient true cholinesterases, DjChE provides insight into the evolution of a hybrid enzyme before the separation into distinct AChE and BChE enzymes found in higher vertebrates. The sensitivity of DjChE to OPs and capacity for reactivation validate the use of planarians for OP toxicology studies.

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Section: Discussionmentioning

confidence: 99%

Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation

et al. 2016

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“…Most vertebrates have one to two genes encoding AChE or butyrylcholinesterase (BChE) (Pezzementi and Chatonnet ; Pezzementi et al . ). In insects, there are one or two AChE genes ( ace1, ace2 ), of which at least one plays a major role in the central cholinergic nervous system (Huchard et al .…”

Section: Number Of Cholinesterase Genes In Animalsmentioning

confidence: 97%

Natural genomic amplification of cholinesterase genes in animals

Chatonnet

Lenfant

Marchot

et al. 2017

Journal of Neurochemistry

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Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases. Natural amplification of cholinesterase genes was first found to occur in some cancer cells and in insect species subjected to evolutionary pressure by insecticides. Analysis of the complete genome sequences of numerous representatives of the various metazoan phyla show that moderate amplification of cholinesterase genes is not uncommon in molluscs, echinoderms, hemichordates, prochordates or lepidosauria. Amplification of acetylcholinesterase genes is also a feature of parasitic nematodes or ticks. In these parasites, over-production of cholinesterase-like proteins in secreted products and the saliva are presumed to have effector roles related to host infection. These amplification events raise questions about the role of the amplified gene products, and the adaptation processes necessary to preserve efficient cholinergic transmission.

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Identification, characterization and expression analyses of cholinesterases genes in Yesso scallop (Patinopecten yessoensis) reveal molecular function allocation in responses to ocean acidification

et al. 2021

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Molecular characterization of an acetylcholinesterase from the hemichordate Saccoglossus kowalevskii

Cited by 3 publications

References 57 publications

Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation

Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation

Natural genomic amplification of cholinesterase genes in animals

Identification, characterization and expression analyses of cholinesterases genes in Yesso scallop (Patinopecten yessoensis) reveal molecular function allocation in responses to ocean acidification

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