Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi

Mechanism of stereoselective interaction between butyrylcholinesterase and ethopropazine enantiomers (CROSBI ID 171706)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Šinko, Goran ; Kovarik, Zrinka ; Reiner, Elsa ; Simeon–Rudolf, Vera ; Stojan, Jure Mechanism of stereoselective interaction between butyrylcholinesterase and ethopropazine enantiomers // Biochimie, 93 (2011), 10; 1797-1807. doi: 10.1016/j.biochi.2011.06.023

Podaci o odgovornosti

Šinko, Goran ; Kovarik, Zrinka ; Reiner, Elsa ; Simeon–Rudolf, Vera ; Stojan, Jure

engleski

Mechanism of stereoselective interaction between butyrylcholinesterase and ethopropazine enantiomers

Stereoselectivity of reversible inhibition of butyrylcholinesterase (BChE ; EC 3.1.1.8) by optically pure ethopropazine [10–(2–diethylaminopropyl)phenothiazine hydrochloride] enantiomers and racemate was studied with acetylthiocholine (0.002–250 mM) as substrate. Molecular modelling resulted in the reaction between BChE and ethopropazine starting with the binding of ethopropazine to the enzyme peripheral anionic site. In the next step ethopropazine 'slides down' the enzyme gorge, resulting in interaction of the three rings of ethopropazine through π–π interactions with W82 in BChE. Inhibition mechanism was interpreted according to three kinetic models: A, B and C. The models differ in the type and number of enzyme–substrate, enzyme–inhibitor and enzyme–substrate–inhibitor complexes, i.e. presence of the Michaelis complex and/or acetylated BChE. Although, all three models reproduced well the BChE activity in absence of ethopropazine, model A was poor in describing inhibition with ethopropazine, while models B and C were better, especially for substrate concentrations above 0.2 mM. However model C was singled out because it approaches fulfilment of the one step–one event criteria, and confirms the inhibition mechanism derived from molecular modelling. Model C resulted in dissociation constants for the complex between BChE and ethopropazine: 61, 140 and 88 nM for R–enantiomer, S–enantiomer and racemate, respectively. The respective dissociation constants for the complexes between acetylated BChE and ethopropazine were 268, 730 and 365 nM. Butyrylcholinesterase had higher affinity for R–ethopropazine.

ethopropazine enantiomers; butyrylcholinesterase; kinetic model; stereoselectivity

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o izdanju

93 (10)

2011.

1797-1807

objavljeno

0300-9084

10.1016/j.biochi.2011.06.023

Povezanost rada

Kemija

Poveznice
Indeksiranost