engleski

Quantum Chemical Investigation of Intermediates in Enzyme Catalyzed Hydrolysis

A combined quantum chemical (Hartree&#8211 ; ; ; Fock, HF/3&#8211 ; ; ; 21G*) and semiempirical (AM1 and PM3) study of the formation of tetrahedral intermediates at the active site of butyrylcholinesterase (BChE) is presented. Geometry optimizations were carried out for the benzoate esters of (R)- and (S)-quinuclidin-3-ol as well as for their N-methyl analogues, for an assumed active site model of BChE. The model consists of three main parts, i. e. the catalytic triad (Ser200, His440 and Glu327), the hydrophobic pocket and an electrostatic region of the active site of BChE. The obtained results indicate interactions between the enzyme and investigated compounds. It seems that strong hydrogen bonds exist between backbone nitrogen atoms (Gly118 and Gly119) and the negatively charged oxygen atom of all compounds. It is confirmed that hydrolysis is in an appreciable extent affected by the geometrical orientation of substrates at the active site, as well [1]. Energy of the optimized systems is lower for (R)- than for (S)-enantiomers which is in good agreement with experimental data [1, 2]. [1] I. Primožič, T. Hrenar, S. Tomić and Z. Meić, J. Phys. Org. Chem., 15 (2002) 1-8. [2] I. Primožič, T. Hrenar, S. Tomić and Z. Meić, First Central European Conference CHEMISTRY TOWARDS BIOLOGY Portorož, Slovenia, 8 - 12 September 2002, poster presentation

butyrylcholinesterase; esters of quinuclidin-3-ol; molecular modeling

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