Literature summary for 3.1.1.7 extracted from

Bester, S.M.; Guelta, M.A.; Cheung, J.; Winemiller, M.D.; Bae, S.Y.; Myslinski, J.; Pegan, S.D.; Height, J.J.
Structural insights of stereospecific inhibition of human acetylcholinesterase by VX and subsequent reactivation by HI-6 (2018), Chem. Res. Toxicol., 31, 1405-1417 .

Activating Compound

Activating Compound	Comment	Organism	Structure
HI-6	chemical mechanism by which HI-6 reactivates enzyme hAChE after inhibition with nerve agent VX, binding mode ate the active site and structure, overview. The amine of the acetamide group of HI-6 in the HI-64 conformation positions itself to optimize hydrogen-bonding interactions with Asp74 and Tyr72. This positioning of the acetamide group and connected pyridinium ring is intriguing as the oxime-containing pyridinium ring's position is similar to that observed in the HI-62 conformation found in the hAChE-HI-6 structure	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
gene ACHE, recombinant expression of His8-tagged enzyme comprising amino acid sequence 1-574 (preprocessed protein numbering which includes the native secretion signal) in HEK-293-H cells	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant His8-tagged enzyme in apoform or ligand-bound structures, sitting drop vapor diffusion, mixing of 16 mg/ml protein in 10 mM HEPES, pH 7.0, and 10 mM NaCl with crystallization solution containing 15-21% PEG 3350 and 0.17-0.21 M potassium nitrate, 22°C, 5-8 days, crystals of ligand (e.g. inhibitors or HI-6) in complex with hAChE are obtained by soaking apo crystals at 22°C in crystallization buffer accompanied by 20-25% ethylene glycol and specific concentrations of each ligand for individually designated periods of time, X-ray diffraction structure determination and analysis at 2.26-2.44 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant His8-tagged enzyme in apoform or ligand-bound structures, sitting drop vapor diffusion, mixing of 16 mg/ml protein in 10 mM HEPES, pH 7.0, and 10 mM NaCl with crystallization solution containing 15-21% PEG 3350 and 0.17-0.21 M potassium nitrate, 22°C, 5-8 days, crystals of ligand (e.g. inhibitors or HI-6) in complex with hAChE are obtained by soaking apo crystals at 22°C in crystallization buffer accompanied by 20-25% ethylene glycol and specific concentrations of each ligand for individually designated periods of time, X-ray diffraction structure determination and analysis at 2.26-2.44 A resolution

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
ethyl((2-[bis(propan-2-yl)amino]ethyl)sulfanyl)-(methyl)phosphinate	VX, stereospecific inhibition of the enzyme by VX and subsequent reactivation by HI-6, structural analysis, overview	Homo sapiens
additional information	organophosphates covalently modify acetylcholinesterase catalytic serine leading to inhibition and in most cases can result in additional processes that age the enzyme	Homo sapiens
O-pinacolyl methylphosphonofluoridate	i.e. soman	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
acetylcholine + H2O	Homo sapiens	-	choline + acetate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P22303	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His8-tagged enzyme from HEK-293-H cells by affinity chromatography and dialysis	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
acetylcholine + H2O	-	Homo sapiens	choline + acetate	-	?

Synonyms

Synonyms	Comment	Organism
AChE	-	Homo sapiens
hAChE	-	Homo sapiens

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
additional information	-	additional information	inhibition kinetics	Homo sapiens