Naslov
Active site mutant acetylcholinesterase interactions with 2-PAM, HI-6, and DDVP

Autori
Kovarik, Zrinka ; Ciban, Nikolina ; Radić, Zoran ; Simeon-Rudolf, Vera ; Taylor, Palmer

Izvornik
Biochemical and Biophysical Research Communications (0006-291X) 342 (2006); 973-978

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

Ključne riječi
antidotes; acetylcholinesterase; butyrylcholinesterase; reactivation; reversible inhibition; 2-PAM; HI-6; phosphorylation

Sažetak
We used mouse recombinant wild-type acetylcholinesterase (AChE ; EC 3.1.1.7), butyrylcholinesterase (BChE ; EC 3.1.1.8), and AChE mutants with mutations (Y337A, F295L, F297I, Y72N, Y124Q, W286A) that resemble residues found at structurally equivalent positions in BChE, to find the basis for divergence between AChE and BChE in following reactions: reversible inhibition by two oximes, progressive inhibition by the organophosphorus compound DDVP and oxime-assisted reactivation of the phosphorylated enzymes. The inhibition enzyme-oxime dissociation constants of AChE w.t. were 150 and 46 &micro ; ; M, of BChE 340 and 27 &micro ; ; M for 2-PAM and HI-6, respectively. Introduced mutations lowered oxime binding affinities for both oximes. DDVP progressively inhibited cholinesterases yielding symmetrical dimethylphosphorylated enzyme conjugates at rates between 104 and 105 min-1M-1. A high extent of oxime-assisted reactivation of all conjugates was achieved, but rates by both oximes were up to 10 times slower for phosphorylated-mutants than for AChE w.t..

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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