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E V Rozengart

Publications and source records attributed to E V Rozengart.

At least 19 recordsLinked to original sources
PubMed1995

[Conformational differences in the sorption of choline ligands at the active site of acetylcholinesterase].

All the relatively stable conformers of acetylcholine, acetylthiocholine, and Rp- and Sp-enantiomers of the thiocholine-containing inhibitor of acetylcholine esterase, (CH3)2CHO(CH3)P(O)SCH2CH2N+(CH3)3, were calculated by the method of molecular mechanics. The population and the distances between functional atoms were determined for the relatively stable conformers. For the inhibitors, the accessibility of the phosphorus atom for interaction with the hydroxyl group of the Ser200 residue was determined. A computer model is proposed for the productive sorption of acetylcholine. The model assumes the contact of acetylcholine in the active center the hydroxyl group of the Ser200 residue, with the group behaving as a donor of H-bond, and also with the trimethylammonium sorptive segment. Among the organophosphorus inhibitors studied there are no relatively stable conformers that would be complementary to the sorptive site of the substrate, the choline head of the inhibitor cannot be sorbed at the trimethylammonium segment of the active center. An explanation was given for the stereospecificity of the studied enantiomers of an organophosphorus inhibitor within the limits of the proposed model.

Acetylcholinesterase↗
PubMed1992

[Dependence of anti-acetylcholinesterase effectiveness of phosphoorganic inhibitors on the accessibility of the phosphorus atom].

All equilibrium conformations of 12 anti-acetylcholinesterase organophosphorus inhibitors were calculated by the molecular mechanics method. The accessibility of the phosphorus atom of the inhibitors for interactions with the nucleophilic group at the enzyme active centre was estimated. The conformers with the phosphorus atom sterically accessible from the side opposite to the breaking ester bond were classified as productive. A correlation was revealed between the activity of the inhibitors and the population of their productive conformation.

Acetylcholinesterase↗
PubMed1989

[Determination of productive conformations of acetylcholinesterase substrates using theoretical conformational analysis].

All equilibrium conformations of twenty-three acetylcholinesterase effectors were calculated by the molecular mechanics method, nonbonded interactions, torsion energy and energy of bond angles deformation being taken into account. In a series of conformationally flexible derivatives of acetylcholine the correlation was found between hydrolysis rate and population of the completely extended tt-conformation. In a series of cyclic analogues of acetylcholine the high hydrolysis rate occurs only for substrates sterically corresponding to tt-conformation of acetylcholine with regard to disposition of ammonium group, carbonyl oxygen and carbonyl carbon. The hydrolysis rate of acetylcholine derivatives with elongated chain between acetyl and cationic groups is directly proportional to the population of the conformations similar to tt-conformation of acetylcholine. It is concluded that tt-conformation of acetylcholine is productive for acetylcholinesterase hydrolysis.

Acetylcholinesterase↗
PubMed1981

[Interaction of frog brain cholinesterase with some reversible ammonium inhibitors].

The effects of some ammonium compounds diiodomethylate acetate (I), propionate (II), butyrate (III), valeriate (IV) N-hydroxyethylanabasine, tetramethylammonium, tetraethylammonium and acetylcholine amide analog derivatives (V-VIII) on acetylthiocholine hydrolysis by cholinesterase from frog brain, acetylcholinesterase from human erythrocytes and butyryl cholinesterase from horse blood serum were studied. Cholinesterase from frog brain possesses a lower sensitivity to the inhibitors than does the mammalian enzyme. Significant conformational changes of the inhibitor molecule, i. e. transition from trans-conformation (V) to the fixed gosh-conformation (VII), have no effect on the anticholinesterase activity of these compounds. A method for evaluation of effectivity of different types of the reversible inhibitors is proposed.

Animals↗
PubMed1978

[Inhibition of acetylcholinesterase hydrolysis of cationic substrates by the reaction product].

The kinetics of acetylcholinesterase-catalyzed hydrolysis of the two cationic substrates (I and II in Russian text) was analyzed by means of the integrated Michaelis equation (3). The constants kII, kcat Km and the enzyme-product complex dissociation constant Ki were determined. (Table 1). It was shown that acetylcholine (II) binds to to the enzyme active center more effectively than the alcohol product of its hydrolysis. In case of the pipecholine derivative (I) reversed situation occurs. The different dependence of the ester substrate and appropriate alcohol binding effectiveness upon the reagent structure indicates the dissimilar location of the molecules in the active center of acetylcholinesterase. Some structural implications of the enzyme active center were discussed.

Acetylcholine↗