The Cholinesterases: From Genes to Proteins

Taylor, Palmer; Radić, Zoran

doi:10.1146/annurev.pa.34.040194.001433

Cited by 650 publications

(435 citation statements)

References 67 publications

Supporting

Mentioning

407

Contrasting

Unclassified

Order By: Relevance

“…SBC3 does not provoke an enhanced immune response as indicated by the lack of an increase in the haemocyte density and the expression of antimicrobial and immune related peptides. A number of proteins were shown to decrease in abundance in larvae that received SBC3 and these included carboxylesterase (spot 3, Table 1) which has physiological functions in neurotransmitter degradation, hormone and pheromones specific metabolism, detoxification, defense and behavior (Vogt et al 1985;Taylor and Radic 1994), 27 kDa haemolymph protein (spot 2) which is secreted into the haemolymph as a signal molecule (Kelly and Kavanagh 2011) and apolipophorin-3 (spot 8) which functions in the innate immune response (Gupta et al 2010). Spot 6, hypothetical protein YQE_03765 partial, was increased in abundance in larvae that received SBC3 and functions as a death domain protein with roles in apoptosis, immune defense, and immune signalling (Lahm et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Assessment of in vivo antimicrobial activity of the carbene silver(I) acetate derivative SBC3 using Galleria mellonella larvae

et al. 2014

View full text Add to dashboard Cite

The antimicrobial drug candidate 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate (SBC3) was evaluated for its ability to function in vivo using larvae of Galleria mellonella. A SBC3 concentration of 25 lg/ml inhibited the growth of Staphylococcus aureus by 71.2 % and Candida albicans by 86.2 % in vitro. Larvae inoculated with 20 ll of SBC3 solution showed no ill effects up to a concentration of 250 lg/ml but administration of 500 lg/ml resulted in a 40 % reduction in larval survival and administration of a dose of 1,000 lg/ml resulted in total larval death at 24 h. Larvae inoculated with S. aureus or C. albicans and subsequently administered SBC3 showed increased survival. Administration of SBC3 to larvae did not boost the insect immune response as indicated by lack of an increase in the density of circulating haemocytes (immune cells). The abundance of a number of proteins involved in the insect immune response was reduced in larvae that received 20 ll SBC3 solution of 100 lg/ml. This is the first demonstration of the in vivo activity of SBC3 against S. aureus and C. albicans and demonstrates that SBC3 does not stimulate a non-specific immune response in larvae.

show abstract

Section: Discussionmentioning

confidence: 99%

Assessment of in vivo antimicrobial activity of the carbene silver(I) acetate derivative SBC3 using Galleria mellonella larvae

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The biological importance of AChE-catalyzed hydrolysis is manifested in the rapid termination of the neuronal impulse that occurs when acetylcholine (ACh) is released into the synaptic cleft. AChE rapidly hydrolyzes ACh into acetic acid and choline at extremely fast turnover rates [Taylor and Radic, 1994]. …”

mentioning

confidence: 99%

“…More complex "asymmetric" isoforms are made up of multiple tetramers tethered by a collagen tail. Most isoforms are found in the central and peripheral nervous systems [Taylor and Radic, 1994;Soreq and Seidman, 2001]. Isoforms have also been characterized in hematopoietic cells, as well as in tumor cells [Karpel et al, 1994;Nechushtan et al, 1996;Perry et al, 2002].…”

mentioning

confidence: 99%

Differential localization of acetylcholinesterase in neuronal and non‐neuronal cells

Thullbery

Cox

Schule

et al. 2005

J of Cellular Biochemistry

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) expression is regulated in cell types at the transcriptional and translational levels. In this study, we characterized and compared AChE catalytic activity, mRNA, protein expression, and protein localization in a variety of neuronal (SH-SY5Y neuroblastoma and primary cerebellar granule neurons (CGN)) and non-neuronal (LLC-MK2, HeLa, THP-1, and primary astrocytes) cell types. All cell lines expressed AChE catalytic activity; however the levels of AChE-specific activity were higher in neuronal cells than in the non-neuronal cell types. CGN expressed significantly more AChE activity than SH-SY5Y cells. All cell lines analyzed expressed AChE protein at equivalent levels, as well as mRNA splice variants. Localization of AChE was characterized by immunofluorescence and confocal microscopy. SH-SY5Y, CGN, and nerve-growth factor-differentiated PC-12 cells exhibited a pattern of AChE localization characterized as diffuse in the cytoplasm and punctate staining along neurites and on the plasma membrane. The localization in HeLa, LLC-MK2, fibroblasts, and undifferentiated PC-12 cells was significantly different than in neuronal cells-AChE was intensely localized in the perinuclear region, without staining near or on the plasma membrane. Based on the evidence presented here, we hypothesize that the presence of AChE protein doesn't correlate with catalytic activity, and the diffuse cytoplasmic and plasma membrane localization of AChE is a property of neuronal cell types. Keywords acetylcholinesterase; confocal microscopy; cerebellar granule neuron; neuroblastoma; SH-SY5Y; HeLa; PC-12 Acetylcholinesterase (AChE) belongs to the serine hydrolase family that contains the α/β hydrolase fold as a common structural element [Ollis et al., 1992]. The catalytic active site of AChE is made up of a precise arrangement of active site functional groups that catalyze the hydrolytic breakdown of esters that bear quaternary ammonium groups. The biological importance of AChE-catalyzed hydrolysis is manifested in the rapid termination of the neuronal impulse that occurs when acetylcholine (ACh) is released into the synaptic cleft. AChE rapidly hydrolyzes ACh into acetic acid and choline at extremely fast turnover rates [Taylor and Radic, 1994].

show abstract

“…In cases where [7,13,14]. Although binding of PAS ligands was shown to modifications of the loop sequence had some effect on reactivity, affect the conformation of the active center over 15 years the effects could be attributed to an altered position of residue ago [17,25], the actual mechanism of this modulation was Trp-86 supporting the proposed coupling between the structure of only recently proposed, suggesting the involvement of a conthe f2 loop and the positioning of the Trp-86 indole moiety, in formational transition of residue . Residue Trp-86 catalytic activity and in aliosterism, which in its active conformation is the main element of the classical 'anionic subsite ' [6,10,11,26,27] ).…”

mentioning

confidence: 99%

“…Residue Trp-86 catalytic activity and in aliosterism, which in its active conformation is the main element of the classical 'anionic subsite ' [6,10,11,26,27] ). In the case of lipases, X-ray crystallographic together with kinetic studies of the AChE muteins with substudies of free versus complexed structures show that the Lba,2 strates and reversible inhibitors [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. However, the location loop is one of the most mobile structural elements [18,22,32].…”

mentioning

confidence: 99%

Structural modifications of the Ω loop in human acetylcholinesterase

et al. 1996

View full text Add to dashboard Cite

ble back door path for product release have been suggested Abstract Conformational mobility of the surface [~ loop (Cys-69-Cys-96) in human acetylcholinesterase (HuAChE) was [20]. Subsequently, it was shown, by septuple replacement of recently implicated in substrate accessibility to the active center negatively charged amino acids, that electrostatic attraction and in the mechanism of aHosteric modulation of enzymatic does not contribute to the catalytic rate of the enzyme [21]. activity. We therefore generated and kinetically evaluated the In addition, mutagenesis of key residues located along the following modifications or replacements in HuAChE: (a) putative back door channel does not support its proposed residues at the loop ends, (b) residues involved in putative role in AChE activity which is located 20 A away from the active center and has either limited or no effect on enzyme reactivity. These results been recently characterized by site-directed mutagenesis suggest that unlike the case of lipase, the ~ loop in the HuAChE is not involved in large lid-like displacements. In cases where [7,13,14]. Although binding of PAS ligands was shown to modifications of the loop sequence had some effect on reactivity, affect the conformation of the active center over 15 years the effects could be attributed to an altered position of residue ago [17,25], the actual mechanism of this modulation was Trp-86 supporting the proposed coupling between the structure of only recently proposed, suggesting the involvement of a conthe f2 loop and the positioning of the Trp-86 indole moiety, in formational transition of residue . Residue Trp-86 catalytic activity and in aliosterism, which in its active conformation is the main element of the classical 'anionic subsite ' [6,10,11,26,27] ). In the case of lipases, X-ray crystallographic together with kinetic studies of the AChE muteins with substudies of free versus complexed structures show that the Lba,2 strates and reversible inhibitors [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. However, the location loop is one of the most mobile structural elements [18,22,32]. of the active center at the bottom of a deep and narrow Simulated annealing experiments of HuAChE suggest that, 'gorge' and the crystallographic dimensions of this gorge also for this enzyme, a large segment of the Lb3,2 loop is the pose an intriguing question regarding the substrate and ligand most mobile part of the molecule [33]. Furthermore, this moaccess to the catalytic site [18]. In addition, the structure rebility was shown to induce the conformational transitions of veals an uneven overall distribution of negative charge giving residue Trp-86 and to modify the dimensions of the active site rise to a large electrostatic dipole, aligned along the active site gorge rendering it more accessible to inbound ligands [28,33]. gorge [19]. Such a dipole would draw the positively chargedTo further test the notion that the dynamic behavior of the substrate down the gorge, however, it could also interfere with ...

show abstract

The Cholinesterases: From Genes to Proteins

Cited by 650 publications

References 67 publications

Assessment of in vivo antimicrobial activity of the carbene silver(I) acetate derivative SBC3 using Galleria mellonella larvae

Assessment of in vivo antimicrobial activity of the carbene silver(I) acetate derivative SBC3 using Galleria mellonella larvae

Differential localization of acetylcholinesterase in neuronal and non‐neuronal cells

Structural modifications of the Ω loop in human acetylcholinesterase

Contact Info

Product

Resources

About