Structural Bases for Selectivity of Butyrylcholinesterase towards Enantiomeric Quinuclidin-3-yl Benzoates: a Quantum Chemical Study
| Autor: | Ines Primožič, Hrenar, T., Tomić, S., Meić, Z. |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: | |
| Zdroj: | Scopus-Elsevier Croatica Chemica Acta Volume 76 Issue 1 |
| ISSN: | 0011-1643 1334-417X |
| Popis: | In order to explain different rates of hydrolysis of (R)- and (S)-quinuclidin-3-yl benzoates and benzoylcholine catalyzed with butyrylcholinesterase, semiempirical PM3 calculations were performed with an assumed active site model of human BChE (20 amino acids). The contributions of different protein residues to the stabilization of Michaelis complexes and tetrahedral intermediates were analyzed. It was shown that the hydrolyses rates of quinuclidinium enantiomers are in an appreciable extent affected by the existence or absence of the hydrogen bond between the quinuclidinium N+-H group and the protein residues. The calculations indicated that the better stabilization of quinuclidinium moiety in the Michaelis complex than in tetraherdal intermediate is the main reason for a greater barrier and a slower reaction rate of the (R)-enantiomer of quinuclidinium esters compared to benzoylcholine. In the case of (S)-enantiomer, the calculation indicated that the barrier for the substrate reorientation from a favourable, but non-productive binding to a productive one, significantly influence the rate of hydrolysis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|