Literature summary for 3.1.1.8 extracted from

Meirer, K.; Glatzel, D.; Kretschmer, S.; Wittmann, S.K.; Hartmann, M.; Bloecher, R.; Angioni, C.; Geisslinger, G.; Steinhilber, D.; Hofmann, B.; Fuerst, R.; Proschak, E.
Design, synthesis and cellular characterization of a dual inhibitor of 5-lipoxygenase and soluble epoxide hydrolase (2016), Molecules, 22, 45.

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme human BChE in complex with the reversible ligands, decamethonium, thioflavin T, propidium, huprine, and ethopropazine, crystals of the BChES2-propidium complex were grown by cocrystallization in the presence of 1 mM ligand. The structure of the complex is solved at 3.0 A resolution, the structure of enzyme-decamethonium is solved at 2.3 A resolution, crystals of the BChECHO-ethopropazine complex are grown by cocrystallization in the presence of 1 mM ligand, the structure is solved at 2.35 A resolution	Homo sapiens

Crystallization (Comment)

Organism

purified enzyme human BChE in complex with the reversible ligands, decamethonium, thioflavin T, propidium, huprine, and ethopropazine, crystals of the BChES2-propidium complex were grown by cocrystallization in the presence of 1 mM ligand. The structure of the complex is solved at 3.0 A resolution, the structure of enzyme-decamethonium is solved at 2.3 A resolution, crystals of the BChECHO-ethopropazine complex are grown by cocrystallization in the presence of 1 mM ligand, the structure is solved at 2.35 A resolution

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(7R,11R)-huprine 19	binding structure from analysis of the crystal structure	Homo sapiens
(7S,11S)-huprine W	binding structure from analysis of the crystal structure	Homo sapiens
decamethonium	binding structure from analysis of the crystal structure determined at 2.3 A resolution, overview. Decamethonium spans the gorge of BChE	Homo sapiens
edrophonium	lower inhibition	Homo sapiens
ethopropazine	ethopropazine is a substituted phenothiazine with a marked specificity for BChE. The 9000fold difference in Ki between hAChE and hBChE reflects this specificity, structure from analysis of the crystal structure determined at 2.35 A resolution, overview	Homo sapiens
additional information	determination and analysis of the crystal structures of enzyme-bound ligands	Homo sapiens
propidium	propidium binds very differently to BChE and mostlly fills the gorge due to absence of a blocking Trp residue. The phenanthridinium ring is slotted into the groove of the acyl-binding pocket, with the amino group at interaction distance from Trp231 (2.8 A to the center of the 6-carbon ring) and Ser198-O (3.3 A), and T-stacked to Phe329. The alkyldiethylmethylammonium moiety extends to Trp82 of the A-site at cation-Pi interaction distance (3.1 A between the 6-carbon ring indole center and C5). The second ethyl group of the quaternary center docks against the propidium phenyl group (4 A to aromatic plane), suggesting an intramolecular cation-Pi interaction. The propidium phenyl group is oriented toward the P-site residues Tyr332 and Asp70	Homo sapiens
thioflavin T	binding structure from analysis of the crystal structure, PDB ID 6ESY, inhibition kinetics and thermodynamics, overview	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P06276	-	-

Synonyms

Synonyms	Comment	Organism
hBChE	-	Homo sapiens

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
additional information	-	additional information	ligand dissociation constants and inhibition kinetics	Homo sapiens
0.00043	-	propidium	pH and temperature not specified in the publication	Homo sapiens
0.0008	-	thioflavin T	pH and temperature not specified in the publication	Homo sapiens
0.0045	-	decamethonium	pH and temperature not specified in the publication	Homo sapiens
0.049	-	edrophonium	pH and temperature not specified in the publication	Homo sapiens

General Information

General Information	Comment	Organism
additional information	catalysis takes place in a 20-A deep active site gorge and involves a catalytic triad of serine, histidine, and glutamate residues located near the bottom of the gorge, denoted the acylation or A-site. The region near the rim of the gorge has been denoted the peripheral site or P-site	Homo sapiens