Naslov
Interactions of pyridinium oximes with acetylcholinesterase

Autori
Šinko, Goran ; Brglez, Josipa ; Kovarik, Zrinka

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

Izvornik
10th International Meeting on Cholinesterases, Šibenik, Croatia, Programme and Abstracts / Kovarik, Zrinka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2009, 47-47

ISBN
978-953-95551-3-7

Skup
10th International Meeting on Cholinesterases

Mjesto i datum
Šibenik, Hrvatska, 20.09.2009. - 25.09.2009

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Acetylcholinesterase; Oximes; Reversible inhibition; Molecular modeling

Sažetak
Catalytic activity of acetylcholinesterase (EC 3.1.1.7 ; AChE) was inhibited with oximes HI-6, K114, K127 and K203, and inhibition constants were determined. Dissociation constants for reversible enzyme-inhibitor complex (KI) were determined in the presence of acetylthiocholine. Based on the mixed inhibition model dissociation constants were 0.020 mM for HI-6, 0.0021 mM for K114, 0.175 mM for K127, and 0.036 mM for K203. Therefore, the most potent inhibitor of AChE was K114, while the weakest was K127. Molecular modelling of AChE-oxime complexes was used to determine aminoacid residues of the active site involved in the interactions. Bis-oxime K114 achieved the best stabilisation in the active site due to π -π interaction between its three aromatic rings and Tyr124, Tyr341 and Trp86, and hydrogen bonds formed by its oxime groups. Mono-oximes HI-6 and K203 that inhibited enzyme with similar potency, showed similar position of their pyridinium rings in the active site. K127 also formed several hydrogen bonds with residues of the active site, but due to its long linker more likely was stabilised at the peripheral site (Tyr124).

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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