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Moralev, S. N.; Розенгарт, Е. В.

doi:10.1023/a:1014022311275

Cited by 8 publications

(5 citation statements)

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“…These differences re also observed when testing a limited number of choline substrates [1,3]. The enzyme classification system [4] classifies cholinesterases only into two groups: (1) acetylcholine hydrolases (EC 3.1.1.7), which most rapidly hydrolyse acetylcholine (AC) compared to other choline esters (the reference enzyme of this group is human erythrocytic acetylcholinesterase (ACE)) and (2) acylcholine hydrolases (EC 3.1.1.8), which include all other cholinesterases (the reference enzyme of this group is horse blood serum butyrylcholinesterase (BCE), which most rapidly hydrolyzes butyrylcholine (BC)) [1,3]. Therefore, substrate specificity is the primary (and, in some cases, the key) test to be used for identification of cholinesterase activity of different animals [1].…”

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confidence: 73%

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Differences in substrate specificity of the cholinesterase activity of nervous tissue of squids may be used in taxonomy

Розенгарт

Basova

2004

Dokl Biochem Biophys

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confidence: 73%

“…It is known that the substrate specificity of cholinesterases includes different aspects of reactivity of cholinesterases [1][2][3]. First of all, this is the "classic" dependence of the rate of substrate hydrolysis on the structure of ester molecule [1].…”

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confidence: 99%

Differences in substrate specificity of the cholinesterase activity of nervous tissue of squids may be used in taxonomy

Розенгарт

Basova

2004

Dokl Biochem Biophys

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“…The mutual arrangement of the functionally important atoms (nitrogen, carbonyl oxygen and carbonyl carbon) in all the compounds, except for ( XXXI ) and ( XXXII ), depends on the values of torsion angles in choline fragment: τ 0 (CH 3 …”

Section: Methods Of Calculationmentioning

confidence: 99%

“…AChE is involved in nerve impulse transmission catalyzing hydrolysis of ACh, its natural neurotransmitter, and is a target for the action of organophosphorus inhibitors and neuroparalytic warfare agents [1][2][3][4][5]. The physiological function of BChEs has not clearly determined until now.…”

Section: Introductionmentioning

confidence: 99%

Theoretical Conformational Analysis in the Determination of Productive Conformations of Substrates for Acetylcholinesterase and Butyrylcholinesterase

Belinskaya

Shestakova

2005

Russ J Bioorg Chem

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2 Abbreviations: ACh, acetylcholine; AChE, acetylcholnesterase; BChE, butyrylcholinesterase; and TCA, theoretical conformational analysis. and tested as their substrates and inhibitors, and the values of kinetic constants of their interactions with effectors were determined [6,7]. Therefore, the two esterases can be used as models in studying the principles underlying the action mechanism of the enzymes.A previous TCA of AChE substrates revealed that, of seven stable conformations of ACh, only the completely extended conformation is productive for the enzymatic hydrolysis [10]. It was shown that, in a series of ACh analogues of the general formula R-C(O)O-Ä lk -N + (CH 3 ) 3 , AChE hydrolyses only those analogues that can exist in the stable conformations compatible with the productive conformation of ACh in respect of the mutual arrangement of functionally significant atoms: nitrogen, carbonyl carbon, and carbonyl oxygen [11]. The deviations in distances between functional atoms should not exceed 0.2 Å. This means that, upon the productive sorption in the active site of AChE, the positions of acyl and trimethylammonium moieties of ACh are strictly determined and, hence, the substrate productive conformations could be chosen by the disAbstract -All the equilibrium conformations of 34 analogues of acetylcholine (ACh) with the general formula R-C(O)O-Ä lk -N + (CH 3 ) 3 are calculated by the method of molecular mechanics. In the series R-C(O)O-(CH 2 ) 2 -N + (CH 3 ) 3 , a reliable correlation is found between the molecular volume of the substrate and the rate of its hydrolysis by acetylcholinesterase (AChE); the absence of such a correlation is demonstrated for butyrylcholinesterase (BChE). Theoretical conformational analysis confirms that the completely extended tt conformation of ACh is productive for the hydrolysis by AChE, which agrees with the results of X-ray analysis of AChE. AChE is shown to hydrolyze only those substrates that form equilibrium conformers compatible in the mutual arrangement of trimethylammonium group, carbonyl carbon, and carbonyl oxygen with the tt conformation of ACh; in this case, the rate of substrate hydrolysis depends on the total population of these conformers. A reliable correlation was found between the population of the semifolded ( tg -) conformation of the choline moiety of substrate molecules and rate of their BChE hydrolysis. In a series of CH 3 -C(O)O-A lk -N + (CH 3 ) 3 , the rate of BChE hydrolysis is demonstrated to depend on the total population of conformations compatible in the mutual arrangement of functionally important atoms with the tg -conformation of ACh. The tg -conformation of ACh is concluded to be productive for BChE hydrolysis. Similar orientations of the substrate molecules relative to the catalytic triads of both AChE and BChE are proven to coincide upon the substrate productive sorption in their active sites. It is hypothesized that the sorption stage is rate-limiting in cholinesterase hydrolysis and the enzyme hydrolyzes the ACh molecule in its energetic...

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“…Compound XII, whose molecule is built by the principle of irreversible organophosphorus inhibitors, whereas the silatran group is located in the so-called "eliminated part of the molecule" [1,2], occupies a special place in the group of anticholinesterase silatran derivates. However, the presence of the thionic group [P(S)] determines the reversible inhibition mode for such organophosphorous inhibitors in the case of specific sorption in the region of the esterase center of the catalytic surface of the enzyme [15]. Compound XII inhibited butyrylcholinesterase ten times more effectively than acetylcholinesterase (the second, after compound IX, case of specificity with respect to butyrylcholinesterase among the silatran derivatives).…”

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confidence: 99%

Element-Onium Silatran Derivatives As Reversible Inhibitors of Cholinesterases of Various Origin

Розенгарт

Basova

2005

Dokl Biochem Biophys

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Cited by 8 publications

References 50 publications

Differences in substrate specificity of the cholinesterase activity of nervous tissue of squids may be used in taxonomy

Differences in substrate specificity of the cholinesterase activity of nervous tissue of squids may be used in taxonomy

Theoretical Conformational Analysis in the Determination of Productive Conformations of Substrates for Acetylcholinesterase and Butyrylcholinesterase

Element-Onium Silatran Derivatives As Reversible Inhibitors of Cholinesterases of Various Origin

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