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Acetylcholinesterase
Potential directions of research for pesticide poisoning
1. What is known and relevant to the workshop?
(A Birds Eye View)
Slide 3 to 10 2. Why not AD drugs as antidote on OP poisoning? Slide 11 to 19 3. Our team research: Identification of peptides that could interact with AChE and its relevance Slide 20 to
*As reported for human AChE in the BRENDA enzyme database 1Kryger et al., (1999) Structure Vol 7, No 3, 297-306 2Dvir et al., (2002) Biochemistry Vol 41, 10810-10818 3Harel et al., (1993) PNAS Vol 90, 9031-9035 4Greenblatt et al., (1999) FEBS Letters Vol 463, 321-326 5Bar-on et al., (2002) Biochemistry Vol 41, 3555-3564
DIMETHOXYINDANONE MOIETY
PIPERIDINE MOIETY
BENZYL MOIETY
Disruption of bond between Gly117-Gly118 and formation of new bonds by Gly117 with Gly119 and Ala201
Binds to choline binding site (Trp84) and acyl binding pocket (Phe288 & Phe290)
H-bond with Glu199 Binds with Ser200
Carbamyl moiety linked covalently to Ser200 Disruption of catalytic triad: H440 moves away from E327 Part of inhibitor occupies peripheral anionic site (Trp84, Phe330)
CARBAMYL GROUP
H-bonding with Gly119 & Ala201 Covalent linkage with Ser200
* Mode of drug binding with Torpedo AChE
S-3[1-(DIETHYL AMINO)ETHYL]PHENOL GROUP - stacking with Trp84, Phe330 H-bonding with Gly118
When pretreated with Galantamine, the soman exposed guinea pigs showed no learning impairment and no memory retention deficit. Galantamine prevents both the acute toxicity and the delayed cognitive deficits triggered by soman poison and can be used against other organophosphorous compounds.
Ref: Mamczarz et al., Neurotoxicology. 2011 Dec;32(6):785-98. Epub 2011 Jul 19.