Acetylcholinesterase from <i>Bungarus</i> venom: a monomeric species

Cousin, Xavier; Créminon, Christophe; Grassi, Jacques; Méflah, Khaled; Cornu, Gur; Saliou, B.; Bon, Suzanne; Massoulié, Jean; Bon, Cassian

doi:10.1016/0014-5793(96)00447-4

Cited by 66 publications

(43 citation statements)

References 16 publications

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“…This enzyme has been characterized as a true AChE, possessing the characteristic catalytic activity of AChEs from cholinergic tissues of other species: it hydrolyses acetylcholine faster than propionylcholine or butyrylcholine and it is inhibited by eserine (5). Moreover, the primary sequences of Naja and Bungarus venom AChEs present a strong homology to those of other AChEs, as shown by analysis of partial peptidic sequences (5,6) and by analysis of the complete sequence of Bungarus AChE deduced from cDNA clones (7).…”

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confidence: 93%

Identification of a Novel Type of Alternatively Spliced Exon from the Acetylcholinesterase Gene of Bungarus fasciatus

Cousin¹,

Bon²,

Massoulié³

et al. 1998

Journal of Biological Chemistry

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The venom of the snake Bungarus fasciatus contains a hydrophilic, monomeric species of acetylcholinesterase (AChE), characterized by a C-terminal region that does not resemble the alternative T-or H-peptides. Here, we show that the snake contains a single gene for AChE, possessing a novel alternative exon (S) that encodes the C-terminal region of the venom enzyme, located downstream of the T exon. Alternative splicing generates S mRNA in the venom gland and S and T mRNAs in muscle and liver. We found no evidence for the presence of an H exon between the last common "catalytic" exon and the T exon, where H exons are located in Torpedo and in mammals. Moreover, COS cells that were transfected with AChE expression vectors containing the T exon with or without the preceding genomic region produced exclusively AChE T subunits. In the snake tissues, we could not detect any glycophosphatidylinositol-anchored AChE form that would have derived from H subunits. In the liver, the cholinesterase activity comprises both AChE and butyrylcholinesterase components; butyrylcholinesterase corresponds essentially to nonamphiphilic tetramers and AChE to nonamphiphilic monomers (G 1 na ). In muscle, AChE is largely predominant: it consists of globular forms (G 1 a and G 4 a ) and trace amounts of asymmetric forms (A 8 and A 12 ), which derive from AChE T subunits. Thus, the Bungarus AChE gene possesses alternatively spliced T and S exons but no H exon; the absence of an H exon may be a common feature of AChE genes in reptiles and birds.

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confidence: 93%

Identification of a Novel Type of Alternatively Spliced Exon from the Acetylcholinesterase Gene of Bungarus fasciatus

Cousin¹,

Bon²,

Massoulié³

et al. 1998

Journal of Biological Chemistry

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“…Comprehensive electrophoretic analysis showed molecular homogeneity in mass but not in charge, consistent with variations in the composition of the glycan chains linked to several (or all) of the five consensus sites for N-glycosylation (Figs. 1, A and B, and 2A, black closed circles) (38,41,67). However, all Fab410 and BfAChE isoforms have the capacity to form complexes as assessed from the native PAGE patterns (Fig.…”

Section: Resultsmentioning

confidence: 98%

“…The cationic character of Fab410 is evident. Both BfAChE and Fab410 are homogenous in mass but not in charge, due to heterogeneous N-glycosylation of natural BfAChE (38,67) and nonspecific C-terminal processing of Fab410 by papain (32); however, all isoforms form complexes as assessed by the inhibition curves (D; below) and further verified by analytical gel filtration (not shown). D, inhibition of BfAChE by Elec410 and Fab410 at equilibrium (individual experiments).…”

Section: Resultsmentioning

confidence: 99%

“…The paratope surface is markedly electropositive and confers a clear anisotropic distribution of charges on the Fab410 variable domains (Fig. 3B) with a dipole moment of 780 debyes that points toward the H chain and emerges near Lys 67 in the VH domain (not shown). This feature is consistent with the calculated high pI value (8.1) of Fab410 and its retention close to the cathode in native PAGE (32) (see Fig.…”

Section: In Bourne Et Al (32)mentioning

confidence: 99%

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Crystal Structure of Snake Venom Acetylcholinesterase in Complex with Inhibitory Antibody Fragment Fab410 Bound at the Peripheral Site

Bourne

Renault

Marchot

2015

Journal of Biological Chemistry

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Background: mAb Elec410 inhibits acetylcholinesterase by binding at the active site gorge entrance. Results: Biochemical and structural characterization of Fab410-bound acetylcholinesterase reveals residual catalytic activity, coexisting open/closed states of a back door channel, and a semi-occluded gorge entrance. Conclusion: Bound antibody restricts substrate access through the gorge and may modulate back door opening. Significance: This unique molecular template with high frequency back door opening refines our understanding of acetylcholinesterase catalysis.

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“…Bungarus venom contains 747000 Ellman's units per g of dry venom of AChE-like activity, being one of the richest venoms in this activity [14]. It is non toxic to mice even at very high doses, and does not reinforce the toxicity of other venom components, thus venom enzyme provides an excellent model for analyzing catalytic mechanism of AChE [15]. In the literature there are reports indicating that antidepressants are inhibitors of cholinesterases from different sources [16,17].…”

Section: Introductionmentioning

confidence: 99%

Comparative study of the inhibitory effect of antidepressants on cholinesterase activity inBungarus sindanus(krait) venom, human serum and rat striatum

Ahmed

Batista

Rocha

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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Cholinesterases are divided into two classes based on differences in their substrate specificity and tissue distribution: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes may be inhibited by several compounds, such as antidepressants. The antidepressants paroxetine, imipramine, clomipramine and sertraline inhibited both venom AChE as well as human serum BChE in a concentration-dependent manner but had no effect on AChE in the rat brain striatum. The IC 50 of venom calculated for imipramine was 0.3 mM, paroxetine 0.38 mM, clomipramine 0.34 mM and sertraline 0.35 mM. Analysis of kinetic data indicated that the inhibition caused by sertraline and paroxetine was mixed, i.e. K m values increased and V max decreased in a concentration dependent manner. Imipramine and clomipramine exhibited competitive inhibition, i.e. K m values increased and V max remained constant. The present results suggest that these therapeutic agents used for depression can also be considered as inhibitors of snake venom and human serum cholinesterase.

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Acetylcholinesterase from Bungarus venom: a monomeric species

Cited by 66 publications

References 16 publications

Identification of a Novel Type of Alternatively Spliced Exon from the Acetylcholinesterase Gene of Bungarus fasciatus

Identification of a Novel Type of Alternatively Spliced Exon from the Acetylcholinesterase Gene of Bungarus fasciatus

Crystal Structure of Snake Venom Acetylcholinesterase in Complex with Inhibitory Antibody Fragment Fab410 Bound at the Peripheral Site

Comparative study of the inhibitory effect of antidepressants on cholinesterase activity inBungarus sindanus(krait) venom, human serum and rat striatum

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