5 A cetykholinesterase

Engineering resistance to ‘aging’ of phosphylated human acetylcholinesterase Role of hydrogen bond network in the active center

“…It is therefore not surprising that no aging could be observed with DFPconjugates of these mutants. 4. DISCUSSION Molecular modeling studies of HuAChE and its phosphonylated conjugates implicated several residues, at the active center, in stabilizing the initial OP conjugate ( Fig.…”

“…The OP-ChE conjugates then undergo postinhibitory processes, the nature and extent of which depend upon the structure of the inhibitor and the particular enzyme studied. Spontaneous reactivation, through displacement of the phosphyl moiety (Scheme 1) from the active site, is usually very slow [3]; however, the enzyme can be reactivated by various oxime nucleophiles ('Re' in Scheme 1) [1,4], In certain cases such reactivation is thwarted due to a concomitant unimolecular process termed aging [1,5]. It was proposed that this process consists of dealkylation through alkyl-oxygen bond scission resulting in a formal negative charge in the OP-ChE conjugate (see Scheme 1) [6,7].…”

New substrates of acetylcholinesterase

“…Acetylcholinesterase (ACHE) has been the subject of intensive studies in the last 4 decades [1,2]. Occupying a central role in transmission of nervous signals and being an efficient hydrolase model enzyme, AChE attracted much interest, and a vast number of compounds were studied as substrates and inhibitors of the enzyme, for both theoretical and applied reasons.…”

Alkynyl phosphates are potent inhibitors of serine enzyme

“…Anticholinesterase phosphate and carbamate derivatixes are extensively used as pesticides [1,2]. Inhibitors of este~ases and proteases are applied as chemotherapeutic drugs.…”