Structure-inhibition relationship in the interaction of cholinesterases from mammalian species with bambuterol, haloxon and their leaving groups (CROSBI ID 498046)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Šinko, Goran ; Bosak, Anita ; Kovarik, Zrinka ; Simeon-Rudolf, Vera
engleski
Structure-inhibition relationship in the interaction of cholinesterases from mammalian species with bambuterol, haloxon and their leaving groups
The rate of progressive inhibition of butyrylcholinesterase (BChE ; EC 3.1.1.8) by haloxon (O, O-di-(2-chloroethyl)-O-(3-chloro-4-methylcoumarin-7-yl) phosphate) and bambuterol (5-[2-(tert-butylamino)-1-hydroxyethyl]-m-phenylene-bis(dimethylcarbamate) hydrochloride), reveals differences in inhibition between horse, human and mouse BChE. Inhibition of horse BChE by bambuterol (ki = 2.1 x 105 min-1 M-1) was about 25-fold slower than that of human or mouse BChE, whereas the inhibition of horse BChE by haloxon (ki = 1.2 x 107 min-1 M-1) was about 2-3-fold slower than that of human or mouse BChE. 3-Chloro-7-hydroxy-4-methylcoumarin (CHMC), the leaving group of haloxon, has a similar affinity for both horse and mouse BChE and 100-fold lower affinity for human BChE. Also CHMC has for all studied BChEs higher affinity than terbutaline. Terbutaline, the leaving group of bambuterol, has 9-fold higher affinity for human BChE than for mouse BChE. Haloxon and the planar CHMC are better BChE inhibitors than bambuterol and terbutaline, and this could be explained partially by their less bulky structure and therefore an easier access to the catalytic centre of the enzyme. Horse, human and mouse BChE primary structures were aligned. The alignment showed that horse BChE shares 90 % of amino acid sequence with human BChE and 82 % with mouse BChE. The sequence alignments together with the three-dimensional BChE structure point out that three residues inside the active site at positions 69, 277 and 285 might be important for the differences in the inhibition of these three BChE species.
butyrylcholinesterase; progressive inhibition; reversible inhibition
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Podaci o prilogu
31-31-x.
2004.
objavljeno
Podaci o matičnoj publikaciji
VIIIth International Meeting on Cholinesterases: Program and Abstracts
Talesa, Vincenzo N. ; Antognelli, Cinzia
Perugia: Universita degli Studi di Perugia
Podaci o skupu
VIIIth International Meeting on Cholinesterases
poster
26.09.2004-30.09.2004
Perugia, Italija