Determination of Activity of Cholinesterases

Augustinsson, Klas‐Bertil

doi:10.1002/9780470110409.ch8

Cited by 50 publications

(10 citation statements)

References 190 publications

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“…AcChoEase is inhibited by excess AcCho, whereas BtChoEase is not (4). Recent evidence (36) suggests that the peripheral anionic site and the AcCho-binding site involved in substrate inhibition may be identical.…”

Section: Resultsmentioning

confidence: 99%

“…The principal role of AcChoEase is termination of impulse transmission at cholinergic synapses (2). Although BtChoEase is widely distributed, its biological role is unknown (3); it is so called because it hydrolyzes butyrylcholine (BtCho) at rates similar to or faster than AcCho, whereas AcChoEase hydrolyzes BtCho much more slowly (4). BtChoEase is also known as serum cholinesterase, due to its high concentration in vertebrate serum (3).…”

mentioning

confidence: 99%

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Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis.

Harel

Sussman

Krejci

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

284

224

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Torpedo acetyicholinesterase (AcChoEase, EC 3.1.1.7) and human butyrylcholnesterase (BtChoEase, EC 3.1.1.8), while clearly differing in substrate specificity and sensitivity to inhibitors, possess 53% sequence homology; this permitted modeling human BtChoEase on the basis of the three-dimensional structure of Torpedo AcChoEase. The modeled BtChoEase structure closely resembled that of AcChoEase in overall features. However, six conserved aromatic residues that line the active-site gorge, which is a prominent feature ofthe AcChoEase structure, are absent in BtChoEase. Modeling showed that two such residues, Phe-288 and Phe-290, replaced by leucine and valine, respectively, in BtChoEase, may prevent entrance of butyrylcholine into the acyl-binding pocket. Their mutation to leucine and valine in AcChoEase, by site-directed mutagenesis, produced a double mutant that hydrolyzed butyrylthiocholine almost as well as acetylthiocholine. The mutated enzyme was also inhibited well by the bulky, BtChoEaseselective organophosphate inhibitor (tetraisopropylpyrophosphoramide, iso-OMPA). Trp-279, at the entrance of the activesite gorge in AcChoEase, is absent in BtChoEase. Modeling designated it as part of the "peripheral" anionic site, which is lacking in BtChoEase. The mutant W279A displayed strongly reduced inhibition by the peripheral site-specific ligand propidium relative to wild-type Torpedo AcChoEase, whereas inhibition by the catalytic-site inhibitor edrophonium was unaffected.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis.

Harel

Sussman

Krejci

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

284

224

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“…NTICHOLINESTERASE activity has been dem-A onstrated in several classes of compounds (1)(2)(3). Studies of synthetic compounds showing high anticholinesterase activity have centered around aromatic carbamates (4), alkyl fluorophosphates ( 5 ) , alkyl polyphosphates (6), and recently Funke, Depierre, and Krucker (7) have synthesized a series of highly active bis neostigmine-type analogs.…”

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confidence: 99%

A New Series of Cholinesterase Inhibitors*

Long

Schueler

1954

Journal of the American Pharmaceutical Association (Scientific

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“…Ellman's colorimetry is one method widely adopted in present research. Yet, it defeats in the higher cost of enzyme and the lack of stability during the procedure of colorimetry [5]. Besides the traditional approach, some newer ones have been developed already by many research groups.…”

Section: Introductionmentioning

confidence: 99%

1H nuclear magnetic resonance relaxation investigation of huperzine E binding to acetylcholinesterase

Qiuling

et al. 2007

Front. Chem. China

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In order to search for better acetylcholinesterase (AchE) inhibitors, the binding properties of AchE with huperizine E, which is a derivative of huperzine A, were investigated with 1 H nuclear magnetic resonance ( 1 H NMR) method. The nonselective, selective and double-selective spin-lattice relaxation rates of some protons in huperzine E were acquired in the absence and presence of AchE at a concentration ratio of [ligand]/[protein] = 1 : 0.005. The enhancements of selective relaxation rates of these protons were obvious after adding AchE. The molecular motional correlation times of two pairs of protons, H-1a/H-1b and H-2/H-3, in the bound state at T = 298 K were 11.7 and 9.46 ns respectively, while they were 27.7 and 35.2 ps in the free state. All of these show that huperzine E has high binding affinity with AchE.

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Determination of Activity of Cholinesterases

Cited by 50 publications

References 190 publications

Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis.

Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis.

A New Series of Cholinesterase Inhibitors*

1H nuclear magnetic resonance relaxation investigation of huperzine E binding to acetylcholinesterase

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