Naslov
Interactions of pyridinium oximes with acetylcholinesterase

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

Izvornik
Chemico-biological interactions (0009-2797) 187 (2010), 1/3; 172-176

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
pyridinium oxime; acetylcholinesterase; mixed inhibition; molecular modelling

Sažetak
Catalytic activity of acetylcholinesterase (AChE ; EC 3.1.1.7) was studied in the presence of oximes HI-6, K114, K127 and K203, and inhibition constants were determined for the reversible enzyme-inhibitor complex (KI). Based on the mixed inhibition model, inhibition constants were 0.020 mM for HI-6, 0.0021 mM for K114, 0.175 mM for K127, and 0.036 mM for K203. Molecular modelling of AChE-oxime complexes was used to determine amino acid residues of the active site involved in the interactions. Bis-oxime K114 achieved the best stabilization 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 with Gly121 and Glu285. Mono-oximes HI-6 and K203, which inhibited the enzyme with similar potency, showed similar positions of their pyridinium rings in the active site. The weakest inhibitor, K127, formed also several hydrogen bonds with the active site residues, but due to its long linker it was more likely stabilized at the peripheral site (Tyr124), which could explain lower AChE affinity for this oxime.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

Napomena
Rad je prezentiran na skupu 10th International Meeting on Cholinesterases ; Elsa Reiner, Jean Massoulié, Terrone Rosenberry, Peter Eyer, Gabi Amitai, Zoran Radić, Zrinka Kovarik (ur.).

POVEZANOST RADA