Naslov
Structure-inhibition relationship in the interaction of cholinesterases from mammalian species with bambuterol, haloxon and their leaving groups

Autori
Šinko, Goran ; Bosak, Anita ; Kovarik, Zrinka ; Simeon-Rudolf, Vera

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
VIIIth International Meeting on Cholinesterases: Program and Abstracts / Talesa, Vincenzo N. ; Antognelli, Cinzia - Perugia : Universita degli Studi di Perugia, 2004, 31-31

Skup
VIIIth International Meeting on Cholinesterases

Mjesto i datum
Perugia, Italija, 26.09.2004. - 30.09.2004

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
butirilkolinesteraza; progresivna inhibicija; reverzibilna inhibicija
(butyrylcholinesterase; progressive inhibition; reversible inhibition)

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA