Literature summary for 3.1.1.7 extracted from

Caliandro, R.; Pesaresi, A.; Cariati, L.; Procopio, A.; Oliverio, M.; Lamba, D.
Kinetic and structural studies on the interactions of Torpedo californica acetylcholinesterase with two donepezil-like rigid analogues (2018), J. Enzyme Inhib. Med. Chem., 33, 794-803 .

Application

Application	Comment	Organism
drug development	the simplified DNP derivatives may represent structural templates for the design of lead compounds for a more effective therapeutic strategy against Alzheimer's disease by foreseeing a dual AChE and BACE-1 inhibitory activity	Tetronarce californica

Crystallization (Commentary)

Crystallization (Comment)	Organism
enzyme in complex with inhibitors (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one and (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5-methoxy-2,3-dihydro-1H-inden-1-one, ligands dissolved in 100 mM DMSO, soaking of native crystals at 4°C for 24 h, in a solution containing 2 mM (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one or (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5-methoxy-2,3-dihydro-1H-inden-1-one, 30% PEG 200, 8% DMSO, and 100 mM MES at pH 6.2, X-ray diffraction structure determination and analysis at 2.17.A and 2.25 A resolution, respectively	Tetronarce californica

Crystallization (Comment)

Organism

enzyme in complex with inhibitors (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one and (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5-methoxy-2,3-dihydro-1H-inden-1-one, ligands dissolved in 100 mM DMSO, soaking of native crystals at 4°C for 24 h, in a solution containing 2 mM (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one or (2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5-methoxy-2,3-dihydro-1H-inden-1-one, 30% PEG 200, 8% DMSO, and 100 mM MES at pH 6.2, X-ray diffraction structure determination and analysis at 2.17.A and 2.25 A resolution, respectively

Tetronarce californica

Inhibitors

Inhibitors	Comment	Organism
(2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one	a rigid DNP-like analogue compound, shows mixed-type inhibition	Tetronarce californica
(2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5-methoxy-2,3-dihydro-1H-inden-1-one	a rigid DNP-like analogue compound, shows mixed-type inhibition	Tetronarce californica
donepezil	-	Tetronarce californica
additional information	the DNP rigidification results in a likely entropy-enthalpy compensation with solvation effects contributing primarily to AChE binding affinity. Detailed kinetic study and inhibition mechanism of 1 and 2 with Torpedo californica AChE (TcAChE), enzyme-ligands crystal structure (PDB ID 5E4T) analysis, molecular docking study, overview	Tetronarce californica

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Tetronarce californica	P04058	i.e. Tetronarce californica	-

Purification (Commentary)

Purification (Comment)	Organism
enzyme by affinity chromatography on a mono-(aminocaproyl)-p-aminophenyltrimethylammonium-containing resin	Tetronarce californica

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
acetylcholine + H2O	-	Tetronarce californica	choline + acetate	-	?
acetylthiocholine + H2O	-	Tetronarce californica	thiocholine + acetate	-	?

Synonyms

Synonyms	Comment	Organism
AChE	-	Tetronarce californica
TcAChE	-	Tetronarce californica

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
22	-	assay at room temperature	Tetronarce californica

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7	-	assay at	Tetronarce californica

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism	Structure
0.00001112	-	(2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one	pH 7.0, 22°C	Tetronarce californica
0.00002986	-	(2E)-2-[(1-benzylpiperidin-4-yl)methylidene]-5-methoxy-2,3-dihydro-1H-inden-1-one	pH 7.0, 22°C	Tetronarce californica